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1.
JCO Precis Oncol ; 8: e2400230, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38822761

RESUMEN

PURPOSE: The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples. METHODS: Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263). Three trained pathologists blindly and independently scored slides using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Comprehensive statistical analyses were performed to evaluate analytical concordance. Digital image analysis (DIA) was used to objectively compare the technical performance of each assay by simulating CPS and TAP. RESULTS: Comparable staining patterns were observed with these three PD-L1 assays. Despite discernible variation in staining intensity, reproducible evaluations of PD-L1 positivity were observed. Inter- and intra-assay assessments of all three assays, using either CPS or TAP and the same PD-L1 cutoffs, demonstrated moderate to almost-perfect (interassay Cohen's kappa [κ] range, 0.47-0.83) and substantial to almost-perfect (intra-assay κ range, 0.77-1.00) agreement. Interpathologist assessment exhibited a significant level of concordance (intraclass correlation coefficient ≥0.92). No difference in technical performance was observed using DIA. CONCLUSION: This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC.


Asunto(s)
Antígeno B7-H1 , Inmunohistoquímica , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patología , Neoplasias Gástricas/metabolismo , Antígeno B7-H1/análisis , Inmunohistoquímica/métodos , Masculino , Femenino , Algoritmos
2.
Pol J Pathol ; 75(1): 25-35, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808606

RESUMEN

Small cell lung carcinoma (SCLC) is characterized by rapid growth and an aggressive clinical course. Standard therapy regimes have limited effects on disease course; therefore the prognosis of SCLC is poor. In the current study, the frequency of programmed death ligand 1 (PD-L1) expression in SCLC and its correlation with clinico-pathological features were evaluated. The study included 100 cases of SCLC wherein testing for PD-L1 was done with the SP263 clone on the Ventana benchmark XT system. Cases with > 1% PD-L1 expression in tumour cells or immune cells were categorized as positive. PD-L1 expression was identified in 14% of cases using the cut-off of ≥ 1%. The tumour proportion score was 10% and the immune proportion score was 9.78% using a cut-off of ≥ 1%. PD-L1 positive expression was more frequent in the male population with age > 40 years. All the patients with positive PD-L1 expression were smokers. In the PD-L1 positive group, presence of necrosis was identified in 71.4% of cases and when compared with the PD-L1 negative subgroup this finding was statistically significant (p = 0.010). Personalized targeted therapy for cases of SCLC is still under evaluation. The use of immunotherapeutic targets, such as PD-L1, may help to define a new treatment strategy for SCLC. Development of new treatment strategies may improve prognosis and survival.


Asunto(s)
Antígeno B7-H1 , Biomarcadores de Tumor , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/análisis , Masculino , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Femenino , Persona de Mediana Edad , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Adulto , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Anciano de 80 o más Años , Inmunohistoquímica , Pronóstico
3.
Tunis Med ; 102(4): 223-228, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38746962

RESUMEN

AIM: Our study aimed to perform on Moroccan patients' non-small cell lung carcinoma (NSCLC) concerning the relationship between PD-L1 tumor expression, clinicopathological features and tumor infiltrating immune cells (ICs). METHODS: This is a retrospective study (2019 to 2021) conducted on samples from Moroccan patients with NSCLC at the Pathological Anatomy Laboratory of Ibn Rochd University Hospital in Casablanca. Eligible participants for our study had to meet the following predefined criteria: age ≥18 years, histologically confirmed NSCLC, no prior therapeutic interventions, availability of clinical and pathological data, and a usable tumor sample for determining PD-L1 status. Exclusion criteria applied to patients with other types of lung cancer and unusable tumor samples. The evaluation of tumor and immune expression of PD-L1 was performed using immunohistochemistry (IHC), with the 22C3 clone on the Dako Autostainer Link 48 platform. Tumor PD-L1 expression was categorized into 3 levels: TPS <1% (negative expression), TPS 1-49% (low expression), and TPS ≥50% (high expression). ICs infiltrating the tumor expressing PD-L1 were considered positive when more than 1% of positive ICs were present. RESULTS: Among the 316 analyzed samples, 56.6% showed a negative expression of PD-L1, 16.8% displayed a low expression of PD-L1, and 26.6% exhibited a strong expression. Regarding the histological type, among patients with TPS ≥ 50%, 25.8% had adenocarcinoma. Among patients with TPS ≥ 50%, 24.81% were smokers. PD-L1 was also strongly expressed in the lung (28.2%) and bronchi (26.5%). PD-L1 expression (TPS ≥ 50%) was observed in 35.29% of early-stage patients. Concerning tumor cells (TCs), 27.5% of tumors infiltrated by ICs had TPS ≥ 50%. Furthermore, coexpression of PD-L1 on both TCs and ICs infiltrating the tumor was found in 27.8% of tumors. Statistical analysis demonstrated a significant association between tumor PD-L1 expression and smoking status (P=0.019). However, no significant difference was observed between PD-L1 expression and the presence of ICs infiltrating the tumor (P=0.652), as well as the IHC expression of PD-L1 on ICs (P=0.259). CONCLUSION: Our results demonstrate a significant association between PD-L1 expression and smoking status. However, no significant association was observed between PD-L1 expression and the presence of infiltrating ICs, nor with the IHC expression of PD-L1 on ICs. Our data underscore the importance of participating in the study of specific factors influencing PD-L1 expression in patients with NSCLC.


Asunto(s)
Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Linfocitos Infiltrantes de Tumor , Humanos , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/análisis , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/inmunología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Linfocitos Infiltrantes de Tumor/inmunología , Linfocitos Infiltrantes de Tumor/patología , Linfocitos Infiltrantes de Tumor/metabolismo , Marruecos/epidemiología , Adulto , Inmunohistoquímica , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Anciano de 80 o más Años
4.
JCO Precis Oncol ; 8: e2300556, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38723233

RESUMEN

PURPOSE: Evaluation of PD-L1 tumor proportion score (TPS) by pathologists has been very impactful but is limited by factors such as intraobserver/interobserver bias and intratumor heterogeneity. We developed an artificial intelligence (AI)-powered analyzer to assess TPS for the prediction of immune checkpoint inhibitor (ICI) response in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The AI analyzer was trained with 393,565 tumor cells annotated by board-certified pathologists for PD-L1 expression in 802 whole-slide images (WSIs) stained by 22C3 pharmDx immunohistochemistry. The clinical performance of the analyzer was validated in an external cohort of 430 WSIs from patients with NSCLC. Three pathologists performed annotations of this external cohort, and their consensus TPS was compared with AI-based TPS. RESULTS: In comparing PD-L1 TPS assessed by AI analyzer and by pathologists, a significant positive correlation was observed (Spearman coefficient = 0.925; P < .001). The concordance of TPS between AI analyzer and pathologists according to TPS ≥50%, 1%-49%, and <1% was 85.7%, 89.3%, and 52.4%, respectively. In median progression-free survival (PFS), AI-based TPS predicted prognosis in the TPS 1%-49% or TPS <1% group better than the pathologist's reading, with the TPS ≥50% group as a reference (hazard ratio [HR], 1.49 [95% CI, 1.19 to 1.86] v HR, 1.36 [95% CI, 1.08 to 1.71] for TPS 1%-49% group, and HR, 2.38 [95% CI, 1.69 to 3.35] v HR, 1.62 [95% CI, 1.23 to 2.13] for TPS <1% group). CONCLUSION: PD-L1 TPS assessed by AI analyzer correlates with that of pathologists, with clinical performance also being comparable when referenced to PFS. The AI model can accurately predict tumor response and PFS of ICI in advanced NSCLC via assessment of PD-L1 TPS.


Asunto(s)
Inteligencia Artificial , Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Inhibidores de Puntos de Control Inmunológico , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Antígeno B7-H1/análisis , Masculino , Femenino , Anciano , Persona de Mediana Edad , Adulto , Anciano de 80 o más Años
5.
Clinics (Sao Paulo) ; 79: 100376, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38733690

RESUMEN

OBJECTIVE: This study aimed to explore the effects of Apatinib combined with Temozolomide (TMZ) on the levels of Soluble PD-1 (sPD-1) and Soluble Programmed Death-1 Ligand (sPD-L1) in patients with drug-resistant recurrent Glioblastoma (GB). STUDY DESIGN: A total of 69 patients with recurrent GB from September 2020 to March 2022 were recruited and assigned to the control group (n = 34) and observation group (n = 35) according to different treatment options after tumor recurrence. The control group was treated with TMZ, and the observation group was treated with Apatinib combined with TMZ. Levels of sPD-1 and spd-l1, clinical efficacy, survival time and adverse reactions were observed and compared between the two groups. RESULTS: General data including gender, age, body mass index, and combined diseases indicated no statistical significance between groups (p > 0.05). Before the intervention, sPD-1 and sPD-L1 levels were not significantly different in the two groups (p > 0.05). After interventions, levels of PD-1 and sPD-L1 levels decreased significantly (p < 0.05). The objective remission rate and clinical benefit rate of the observation group were higher and overall survival and progression-free survival were longer than those of the control group (p < 0.05). No significant difference was observed in major adverse reactions among patients (p > 0.05). CONCLUSIONS: Apatinib combined with TMZ is safe and effective in the treatment of recurrent GB. The combined application of the two can reduce the levels of sPD-1 and sPD-L1, which has important clinical application value.


Asunto(s)
Neoplasias Encefálicas , Resistencia a Antineoplásicos , Glioblastoma , Recurrencia Local de Neoplasia , Receptor de Muerte Celular Programada 1 , Piridinas , Temozolomida , Humanos , Temozolomida/uso terapéutico , Femenino , Masculino , Glioblastoma/tratamiento farmacológico , Piridinas/uso terapéutico , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Adulto , Resistencia a Antineoplásicos/efectos de los fármacos , Neoplasias Encefálicas/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Antígeno B7-H1/análisis , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Resultado del Tratamiento
6.
Virchows Arch ; 484(4): 597-608, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38570364

RESUMEN

Assessing programmed death ligand 1 (PD-L1) expression on tumor cells (TCs) using Food and Drug Administration-approved, validated immunoassays can guide the use of immune checkpoint inhibitor (ICI) therapy in cancer treatment. However, substantial interobserver variability has been reported using these immunoassays. Artificial intelligence (AI) has the potential to accurately measure biomarker expression in tissue samples, but its reliability and comparability to standard manual scoring remain to be evaluated. This multinational study sought to compare the %TC scoring of PD-L1 expression in advanced urothelial carcinoma, assessed by either an AI Measurement Model (AIM-PD-L1) or expert pathologists. The concordance among pathologists and between pathologists and AIM-PD-L1 was determined. The positivity rate of ≥ 1%TC PD-L1 was between 20-30% for 8/10 pathologists, and the degree of agreement and scoring distribution for among pathologists and between pathologists and AIM-PD-L1 was similar both scored as a continuous variable or using the pre-defined cutoff. Numerically higher score variation was observed with the 22C3 assay than with the 28-8 assay. A 2-h training module on the 28-8 assay did not significantly impact manual assessment. Cases exhibiting significantly higher variability in the assessment of PD-L1 expression (mean absolute deviation > 10) were found to have patterns of PD-L1 staining that were more challenging to interpret. An improved understanding of sources of manual scoring variability can be applied to PD-L1 expression analysis in the clinical setting. In the future, the application of AI algorithms could serve as a valuable reference guide for pathologists while scoring PD-L1.


Asunto(s)
Inteligencia Artificial , Antígeno B7-H1 , Biomarcadores de Tumor , Variaciones Dependientes del Observador , Humanos , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/metabolismo , Reproducibilidad de los Resultados , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/metabolismo , Carcinoma de Células Transicionales/diagnóstico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias Urológicas/patología , Neoplasias Urológicas/metabolismo , Inmunohistoquímica/métodos , Patólogos , Urotelio/patología , Urotelio/metabolismo
7.
Medicina (B Aires) ; 84(2): 227-235, 2024.
Artículo en Español | MEDLINE | ID: mdl-38683507

RESUMEN

INTRODUCTION: Triple negative breast cancer endophenotype (TNBC) is one of the least frequent and without therapeutic target; therefore we propose to study the correlation of PD-L1 immune checkpoint with the establishment of tumor microenvironment assessed by intratumoral stromal lymphocyte infiltration (TILS) and its importance in clinical practice. METHODS: A retrospective case-control study was performed, with 31 cases of triple-negative infiltrating breast carcinoma and 57 unmatched controls of Luminal A, Luminal B and HER-2 endophenotype seen in one year. The following variables were evaluated: histologic type and grade, PD-L1 expression with clone 22C3, TILS, lymphovascular invasion, tumor size, lymph node involvement and metastasis. Statistical analysis was performed with the chi-square test and Spearman correlation coefficient test. RESULTS: a statistically significant negative correlation was found between TILS and PD-L1 (rho - 0.106, p 0.025), indicating that the higher the expression of PD-L1, the lower the intratumoral lymphocytic infiltration. In the TILS B (10-40% TILS) and C (40-90% TILS) groups where there was a marked intratumoral inflammatory infiltrate, a greater number of patients were negative for PD-L1 (CPS <10) with 16 and 10 cases, respectively. For TNBC cases a negative association coefficient was identified (rho -0.378) with statistical significance (p 0.01). DISCUSSION: The association between TNBC, TILS and PDL1 expression was established, which is important for the establishment of target therapies and the development of precision medicine.


Introducción: El endofenotipo de cáncer de mama triple negativo (TNBC) es uno de los menos frecuentes y sin diana terapéutica, por tanto, se plantea estudiar la correlación del punto de control inmunológico PD-L1 con el establecimiento de microambiente tumoral evaluado por la infiltración linfocitaria intratumoral estromal (TILs) y su importancia en la práctica clínica. Métodos: Se realizó un estudio retrospectivo de casos y controles, con 31 casos de carcinoma infiltrante de la mama triple negativo y 57 controles no pareados de endofenotipo Luminal A, Luminal B y HER-2 atendidos en un año. Se evaluaron las variables: tipo y grado histológico, expresión PD-L1 con el clon 22C3, TILs, invasión linfovascular, tamaño tumoral, compromiso de ganglios linfáticos y metástasis. El análisis estadístico se ejecutó con la prueba de chi cuadrado y prueba de coeficiente de correlación de Spearman. Resultados: Se encontró una correlación negativa estadísticamente significativa entre TILs y PD-L1 (rho - 0.106, p 0.025), indicando que a mayor expresión de PD-L1, es menor la infiltración linfocitaria intratumoral. En los grupos de TILs B (10-40% TILs) y C (40-90% TILs) donde se presenta marcado infiltrado inflamatorio intratumoral se evidenció mayor número de pacientes negativos para PD-L1 (CPS <10) con 16 y 10 casos respectivamente. Para los casos TNBC se logró identificar un coeficiente de asociación negativa (rho -0.378) y con significancia estadística (p 0.01). Discusión: Se estableció la asociación de TNBC, TILs y expresión de PDL1, lo cual es importante para la instauración de terapias diana y el desarrollo de la medicina de precisión.


Asunto(s)
Antígeno B7-H1 , Linfocitos Infiltrantes de Tumor , Neoplasias de la Mama Triple Negativas , Anciano , Femenino , Humanos , Persona de Mediana Edad , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Estudios de Casos y Controles , Linfocitos Infiltrantes de Tumor/inmunología , Estudios Retrospectivos , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/inmunología , Microambiente Tumoral/inmunología
8.
Cancer Rep (Hoboken) ; 7(4): e2057, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38662366

RESUMEN

AIMS: Cervical cancer (CC) is a common malignancy in women, predominantly caused by human papillomavirus. The most subtypes are adenocarcinomas (AC) and squamous cell carcinomas (SCC), which show various features and treatment responses. Programmed death-ligand 1 (PD-L1) and programmed cell death protein 1 (PD-1) as Immune checkpoint molecules, play a role in immune evasion. We investigated PD-L1 expression in AC and SCC of the cervix and explored its link to clinical characteristics. METHODS AND RESULTS: The present cross-sectional research was done between 2016 and 2022 on samples in Shahid Beheshti University of Medical Sciences-affiliated hospitals in Iran. Histological tissue samples of CCs (16 AC and 48 SCC) were assessed, and clinical information was obtained by reviewing their medical documents. PD-L1 expression was evaluated by immunohistochemistry and we used the combined positive score. SCC cases showed a higher (not significant) PD-L1 expression. The PD-L1 expression and clinical characteristics were not significantly correlated in both subgroups. CONCLUSION: Although SCC cases exhibited higher PD-L1 expression, this difference was non-significant. More investigations should highlight the role of PD-L1 in CC and the potential benefits of immunotherapy.


Asunto(s)
Adenocarcinoma , Antígeno B7-H1 , Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Humanos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/metabolismo , Neoplasias del Cuello Uterino/terapia , Femenino , Antígeno B7-H1/metabolismo , Antígeno B7-H1/análisis , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Estudios Transversales , Adenocarcinoma/patología , Adenocarcinoma/metabolismo , Persona de Mediana Edad , Adulto , Adhesión en Parafina , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/análisis , Irán , Anciano , Inmunohistoquímica
9.
Lung ; 202(3): 325-330, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38637361

RESUMEN

PURPOSE: Immunotherapy is a leading approach for treating advanced non-small cell lung cancer (NSCLC) by targeting the PD-1/PD-L1 checkpoint signaling pathway, particularly in tumors expressing high levels of PD-L1 (Jug et al. in J Am Soc Cytopathol 9:485-493, 2020; Perrotta et al. in Chest 158: 1230-1239, 2020). Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a minimally invasive method to obtain tissue for molecular studies, including PD-L1 analysis, in unresectable tumors (Genova et al. in Front Immunol 12: 799455, 2021; Wang et al. in Ann Oncol 29: 1417-1422, 2018). This study aimed to assess the adequacy of PD-L1 assessment in EBUS-TBNA cytology specimens. METHODS: Data was collected retrospectively from patients who underwent EBUS-TBNA between 2017 and 2021 for suspected lung cancer biopsy. Samples positive for NSCLC were examined for PD-L1 expression. EBUS was performed by experienced practitioners, following institutional guidelines of a minimum of five aspirations from positively identified lesions. Sample adequacy for molecular testing was determined by the pathology department. RESULTS: The analysis involved 387 NSCLC cases (149 squamous cell, 191 adenocarcinoma, 47 unspecified). Of the 263 EBUS-TBNA specimens tested for PD-L1, 237 (90.1%) were deemed adequate. While 84% adhered to the protocol, adherence did not yield better results. Significantly higher PD-L1 adequacy was observed in squamous cell carcinomas (93.2%) compared to adenocarcinoma (87.6%). The number of aspirations and sedation type did not correlate with PD-L1 adequacy in either cancer type, but lesion size and location had a significant impact in adenocarcinomas. Adenocarcinoma exhibited higher PD-L1 expression (68%) compared to squamous cell carcinoma (48%). CONCLUSION: EBUS-TBNA offers high yields for assessing immunotherapy markers like PD-L1, with satisfactory adequacy regardless of NSCLC subtype, lesion size, or location.


Asunto(s)
Antígeno B7-H1 , Carcinoma de Pulmón de Células no Pequeñas , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico , Neoplasias Pulmonares , Humanos , Neoplasias Pulmonares/patología , Antígeno B7-H1/metabolismo , Antígeno B7-H1/análisis , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/métodos , Carcinoma de Pulmón de Células no Pequeñas/patología , Masculino , Estudios Retrospectivos , Femenino , Anciano , Persona de Mediana Edad , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/diagnóstico , Anciano de 80 o más Años , Adulto , Broncoscopía/métodos , Adenocarcinoma/patología
10.
BMC Urol ; 24(1): 96, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38658905

RESUMEN

BACKGROUND: A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer. Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse. METHODS: To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era. RESULTS: Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers. PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p = 0.0255) and was even higher in muscle-invasive (pT2-4) carcinomas (29.3%; p < 0.0001). However, within pT2-4 carcinomas, PD-L1 positivity was linked to low pT stage (p = 0.0028), pN0 (p < 0.0001), L0 status (p = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs (p = 0.0073 for tumor cells and p = 0.0086 for inflammatory cells). PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells (p < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001). CONCLUSION: It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.


Asunto(s)
Antígeno B7-H1 , Carcinoma de Células Transicionales , Inhibidores de Puntos de Control Inmunológico , Invasividad Neoplásica , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Antígeno B7-H1/análisis , Antígeno B7-H1/biosíntesis , Masculino , Femenino , Pronóstico , Carcinoma de Células Transicionales/patología , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/metabolismo , Anciano , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Anciano de 80 o más Años , Estudios Retrospectivos
11.
Nanoscale ; 16(18): 8950-8959, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38630023

RESUMEN

Exosomal programmed death ligand-1 (ExoPD-L1) is a vital marker of immune activation in the early stages of tumor therapy and it can inhibit anti-tumor immune responses. However, due to the low expression of ExoPD-L1 in cancer cells, it is difficult to perform highly sensitive assays and accurately differentiate cancer sources. Therefore, we constructed a coaxial dual-path electrochemical biosensor for highly accurate identification and detection of ExoPD-L1 from lung cancer based on chemical-biological coaxial nanomaterials and nucleic acid molecular signal amplification strategies. The measurements showed that the detected ExoPD-L1 concentrations ranged from 6 × 102 particles per mL to 6 × 108 particles per mL, and the detection limit was 310 particles per mL. Compared to other sensors, the electrochemical biosensor designed in this study has a lower detection limit and a wider detection range. Furthermore, we also successfully identified lung cancer-derived ExoPD-L1 by analyzing multiple protein biomarkers expressed on exosomes through the "AND" logic strategy. This sensor platform is expected to realize highly sensitive detection and accurate analysis of multiple sources of ExoPD-L1 and provide ideas for the clinical detection of ExoPD-L1.


Asunto(s)
Antígeno B7-H1 , Técnicas Biosensibles , Técnicas Electroquímicas , Exosomas , Neoplasias Pulmonares , Técnicas Biosensibles/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Humanos , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Exosomas/química , Exosomas/metabolismo , Límite de Detección , Biomarcadores de Tumor/análisis , Línea Celular Tumoral
14.
Cancer Invest ; 42(2): 141-154, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38486421

RESUMEN

We investigated expressions of PD-L1, LAG-3, TIM-3, and OX40L as immune checkpoint proteins, and MSI (repetitive short-DNA-sequences due to defective DNA-repair system) status were analyzed with immunohistochemistry from tissue blocks. Of 83 patients, PD-L1 expression was observed in 18.1% (n = 15) of the patients. None of the patients exhibited LAG-3 expression. TIM-3 expression was 4.9% (n = 4), OX40L was 22.9% (n = 19), and 8.4% (n = 7) of the patients had MSI tumor. A low-to-intermediate positive correlation was observed between PD-L1 and TIM-3 expressions (rho: 0.333, p < 0.01). Although PD-L1 expression was higher in grade 3 NET/NEC, MSI status was prominent in grade 1/2 NET.


Asunto(s)
Antígeno B7-H1 , Neoplasias Gastrointestinales , Receptor 2 Celular del Virus de la Hepatitis A , Proteínas de Punto de Control Inmunitario , Tumores Neuroendocrinos , Neoplasias Pancreáticas , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Reparación del ADN , Neoplasias Gastrointestinales/química , Neoplasias Gastrointestinales/patología , Receptor 2 Celular del Virus de la Hepatitis A/análisis , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Proteínas de Punto de Control Inmunitario/análisis , Proteínas de Punto de Control Inmunitario/metabolismo , Proteína del Gen 3 de Activación de Linfocitos/análisis , Proteína del Gen 3 de Activación de Linfocitos/metabolismo , Tumores Neuroendocrinos/química , Tumores Neuroendocrinos/patología , Ligando OX40/análisis , Ligando OX40/metabolismo , Neoplasias Pancreáticas/química , Neoplasias Pancreáticas/patología , Estudios Retrospectivos , Inmunohistoquímica , Clasificación del Tumor
15.
Abdom Radiol (NY) ; 49(4): 1320-1329, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38436699

RESUMEN

OBJECTIVE: We aimed to explore the correlation between routine computed tomography (CT) imaging features and programmed cell death ligand-1(PD-L1) expression status in gastric cancer and evaluate the predictive value of imaging parameters for this immunotherapy biomarker. MATERIALS AND METHODS: Patients with gastric adenocarcinoma who underwent abdominal CT three-stage enhanced scan and PD-L1 immunohistochemical testing before treatment were retrospectively examined. All diagnoses were confirmed through pathology. According to the expression status of PD-L1, they were divided into the positive (CPS ≥ 5) or negative group (CPS < 5). Baseline CT imaging features were collected. Diagnostic performances of the different variables were evaluated using receiver operating characteristic (ROC) curve. RESULTS: In total, 67 patients (17 women and 50 men; mean age: 59.55 ± 10.22 years) with gastric adenocarcinoma were included in the study. The overall stages, probability of maximum lymph node short diameter > 1 cm and peak of lesion enhancement occurring in the arterial phase were statistically significant between the two groups (p < 0.05). Moreover, the arterial enhancement fraction (AEF) was significantly higher in the positive group than that in the negative group (p < 0.05), and ROC curve analysis showed that the AEF exhibited a high evaluation efficacy (area under the curve [AUC] = 0.724 [95% confidence interval (CI): 0.602-0.826]). The combined parameters had the best diagnostic efficacy (AUC = 0.825 [95%CI: 0.716-0.933]), sensitivity (75.00%), and specificity (81.40%). CONCLUSIONS: These findings confirm a correlation between CT imaging features and PD-L1 expression status in gastric cancer, and AEF may help evaluate high PD-L1 expression and select patients suitable for immunotherapy.


Asunto(s)
Adenocarcinoma , Neoplasias Gástricas , Masculino , Humanos , Femenino , Persona de Mediana Edad , Anciano , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/patología , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Estudios Retrospectivos , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/patología , Tomografía Computarizada por Rayos X
16.
Biosens Bioelectron ; 251: 116104, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38368644

RESUMEN

Exosomal proteins from the parental cells are considered to be promising biomarker sets for precise tumor diagnostics and monitoring. However, the accurate quantitative analysis of low-abundance exosomal proteins remains challenging due to the heterogeneity of clinical samples. Here, we standardized the exosomal concentration with a fluorogenic membrane probe and developed an aptamer-bivalent-cholesterol-mediated Proximity Entropy-driven Exosomal Protein Reporter (PEEPR). The proposed PEEPR enables the in-situ analysis of multiple exosomal proteins by integrating bivalent cholesterol anchor (exosomal lipid bilayer) and aptamer (exosomal proteins) with a proximity entropy-driven circuit. Based on this strategy, we successfully achieved detection limits of 3.9 pg/mL exosomal GPC-3 and 3.4 pg/mL exosomal PD-L1. Notably, the standardization of exosome concentrations is designed to avoid errors due to biological heterogeneity. The results showed that evaluating the levels of exosomal GPC-3 and PD-L1 in clinical samples via this strategy could accurately differentiate healthy individuals, hepatitis B patients, and hepatocellular carcinoma patients. In summary, PEEPR is a promising clinical diagnostic strategy for the quantitative analysis of a variety of tumor-associated exosomal proteins for the precise diagnosis and personalized treatment monitoring of tumors.


Asunto(s)
Técnicas Biosensibles , Carcinoma Hepatocelular , Exosomas , Neoplasias Hepáticas , Humanos , Antígeno B7-H1/análisis , Entropía , Técnicas Biosensibles/métodos , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Exosomas/química
17.
Pathol Res Pract ; 254: 155133, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38306860

RESUMEN

BACKGROUND: Squamous cell carcinoma accounts for > 90% of Head and neck cancers and has a poor 5-year survival rate of only 50%. Immunosuppressive agents like PD-L1 inhibitors have been found to improve survival in many tumour types, including advanced/recurrent head and neck squamous cell carcinoma (HNSCC). The PD-L1 expression in this tumour can also predict clinical outcome. However, this fact still remains to be proven. AIM: The aim was to study the expression of PD-L1 in HNSCC, correlate with clinicopathological parameters and outcome. MATERIAL AND METHOD: This prospective study was conducted between March 2021 to June 2023 in department of Pathology of a tertiary care centre located in northern India. A total of 65 histologically confirmed cases of HNSCC were included. Expression of PD-L1 was determined by immunohistochemistry. The combined positive (CPS) and tumour proportion (TP) scores were calculated. The results were correlated with clinicopathological parameters and outcome using appropriate statistical tools. RESULTS: Considering CPS, 42 (64.6%) cases showed expression of PD-L1. A high score of ≥ 20% was seen in 10 cases (15.4%). PD-L1 expression did not correlate with any of the clinical parameters including age, gender, addiction, site, TNM stage and HPV status. Conventional HNSCC had significantly higher expression of PD-L1. The cases with positive PD-L1 expression had a higher mean survival and a lower mortality, but the difference was not statistically significant. CONCLUSION: PD-L1 expression is more likely to be seen in conventional HNSCC histomorphology. PD-L1 expression is a predictor of better prognosis in HNSCC.


Asunto(s)
Antígeno B7-H1 , Biomarcadores de Tumor , Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Antígeno B7-H1/análisis , Biomarcadores de Tumor/análisis , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Recurrencia Local de Neoplasia , Pronóstico , Estudios Prospectivos , Carcinoma de Células Escamosas de Cabeza y Cuello
18.
Int J Mol Sci ; 25(4)2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38396998

RESUMEN

Next-generation sequencing technologies have started a new era of respiratory tract research in recent years. Alterations in the respiratory microbiome between healthy and malignant conditions have been revealed. However, the composition of the microbiome varies among studies, even in similar medical conditions. Also, there is a lack of complete knowledge about lung-gut microbiome interactions in lung cancer patients. The aim of this study was to explore the lung-gut axis in non-small-cell lung cancer (NSCLC) patients and the associations between lung-gut axis microbiota and clinical parameters (CRP, NLR, LPS, CD8, and PD-L1). Lung tissue and fecal samples were used for bacterial 16S rRNA sequencing. The results revealed, for the first time, that the bacterial richness in lung tumor tissue gradually decreased with an increase in the level of PD-L1 expression (p < 0.05). An analysis of ß-diversity indicated a significant positive correlation between the genera Romboutsia and Alistipes in both the lung tumor biopsies and stool samples from NSCLC patients (p < 0.05). Survival analysis showed that NSCLC patients with higher bacterial richness in their stool samples had prolonged overall survival (HR: 2.06, 95% CI: 1.025-4.17, p = 0.0426).


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Microbioma Gastrointestinal , Neoplasias Pulmonares , Pulmón , Humanos , Antígeno B7-H1/genética , Antígeno B7-H1/análisis , Carcinoma de Pulmón de Células no Pequeñas/microbiología , Carcinoma de Pulmón de Células no Pequeñas/patología , Pulmón/microbiología , Pulmón/patología , Neoplasias Pulmonares/microbiología , ARN Ribosómico 16S/genética
19.
Eur J Nucl Med Mol Imaging ; 51(6): 1582-1592, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38246910

RESUMEN

PURPOSE: Programmed cell death protein ligand 1 (PD-L1) is a crucial biomarker for immunotherapy. However, nearly 70% of patients do not respond to PD-L1 immune checkpoint therapy. Accurate monitoring of PD-L1 expression and quantification of target binding during treatment are essential. In this study, a series of small-molecule radiotracers were developed to assess PD-L1 expression and direct immunotherapy. METHODS: Radiotracers of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were designed based on a 2-methyl-3-biphenyl methanol scaffold and successfully synthesized. Cellular experiments and molecular docking assays were performed to determine their specificity for PD-L1. PD-L1 status was investigated via positron emission tomography (PET) imaging in MC38 tumor models. PET imaging of [68Ga]Ga-D-pep-PMED was performed to noninvasively quantify PD-L1 blocking using an anti-mouse PD-L1 antibody (PD-L1 mAb). RESULTS: The radiosyntheses of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were achieved with radiochemical yields of 87 ± 6%, 82 ± 4%, and 79 ± 9%, respectively. In vitro competition assays demonstrated their high affinities (the IC50 values of [68Ga]Ga-D-PMED, [68Ga]Ga-D-PEG-PMED, and [68Ga]Ga-D-pep-PMED were 90.66 ± 1.24, 160.8 ± 1.35, and 51.6 ± 1.32 nM, respectively). At 120 min postinjection (p.i.) of the radiotracers, MC38 tumors displayed optimized tumor-to-muscle ratios for all radioligands. Owing to its hydrophilic modification, [68Ga]Ga-D-pep-PMED had the highest target-to-nontarget (T/NT) ratio of approximately 6.2 ± 1.2. Interestingly, the tumor/liver ratio was hardly affected by different concentrations of the inhibitor BMS202. We then evaluated the impacts of dose and time on accessible PD-L1 levels in the tumor during anti-mouse PD-L1 antibody treatment. The tumor uptake of [68Ga]Ga-D-pep-PMED significantly decreased with increasing PD-L1 mAb dose. Moreover, after 8 days of treatment with a single antibody, the uptake of [68Ga]Ga-D-pep-PMED in the tumor significantly increased but remained lower than that in the saline group. CONCLUSION: PET imaging with [68Ga]Ga-D-pep-PMED, a small-molecule radiotracer, is a promising tool for evaluating PD-L1 expression and quantifying the target blockade of PD-L1 to assist in the development of effective therapeutic regimens.


Asunto(s)
Acetamidas , Antígeno B7-H1 , Tomografía de Emisión de Positrones , Piridinas , Inmunoterapia , Antígeno B7-H1/análisis , Antígeno B7-H1/antagonistas & inhibidores , Humanos , Animales , Ratones , Línea Celular Tumoral , Células A549 , Compuestos Organometálicos , Radioisótopos de Galio , Acetamidas/química , Piridinas/química
20.
J Clin Pathol ; 77(4): 233-238, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-36650045

RESUMEN

AIMS: In recent years, patients with programmed cell death-Ligand 1 (PD-L1)-positive oesophageal squamous cell carcinoma (OSCC) have been able to benefit from immunotherapy. However, method for improving the treatment efficacy of PD-L1-positive patients is a problem that needs further consideration. Studies on the relationship between human epidermal growth factor receptor 2 (HER2) and PD-L1 expression have recently been reported in certain cancers, but the relationship between PD-L1 and HER2 expression in OSCC is still unclear. METHODS: A total of 263 patients with OSCC were included in the study. PD-L1 protein expression and HER2 protein expression were analysed by immunohistochemistry (IHC), and fluorescence in situ hybridisation (FISH) was performed to assess HER2 gene amplification. The significance of differences between HER2 status, PD-L1 status and clinicopathological parameters was assessed. The relationship between PD-L1 status and HER2 status was examined. RESULTS: Of the 263 OSCC cases, the PD-L1-positive expression rates were 39.2% and 77.2% in OSCC for Tumour Proportion Score (TPS) and Combined Positive Score (CPS), respectively, and PD-L1 expression was associated with the degree of tumour differentiation. The HER2 expression was positive in 24% (63/263) of cases based on IHC and FISH. HER2 expression was not significantly associated with clinicopathological characteristics. PD-L1 TPS expression and CPS expression were significantly positively correlated with HER2 expression in OSCC. CONCLUSIONS: PD-L1 expression was significantly positively correlated with HER2 expression in OSCC. The results provide valuable insight for the future application of HER2-targeted therapy combined with immunotherapy in OSCC.


Asunto(s)
Antígeno B7-H1 , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Neoplasias de la Boca , Receptor ErbB-2 , Humanos , Antígeno B7-H1/análisis , Antígeno B7-H1/metabolismo , Neoplasias Esofágicas/genética , Neoplasias de la Boca/patología , Receptor ErbB-2/metabolismo
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