Tratamiento y evolución de la encefalitis inmunomediada en edad pediátrica, serie de casos / Treatment and outcome of immune-mediated encephalitis in children, a case series

Introducción: La encefalitis por anticuerpos contra el receptor N-metil.D.aspartato (NMDA-R) es un trastorno inflamatorio del sistema nervioso central (SNC) en el cual autoanticuerpos dirigidos hacia la subunidad NR1 del receptor N-metil-D aspartato (NMDA) desarrollan un conjunto de síntomas neuropsiquiátricos, convulsiones y movimientos anormales. El tratamiento recomendado incluye metilprednisolona (MP) y gamaglobulina (IVIg), y/o recambio plasmático terapéutico (RPT); y en caso de no respuesta: rituximab (RTX) y/o ciclofosfamida (CFM). Objetivos: Analizar características clínicas, bioquímicas, electroencefalograma (EEG), resonancia magnética (RM) cerebral, tratamientos recibidos y resultados observados en una serie de pacientes con encefalitis autoinmune (EA) probable o confirmada. Materiales y métodos: Analizamos las historias clínicas de pacientes menores a 17 años que cumplían criterios diagnósticos de Graus (2016) para EA probable, con seguimiento mayor a 6 meses, internados en el Hospital Garrahan entre 2008 y 2023. El diagnóstico se definió por la identificación de anticuerpos anti-NMDAR (N-metil D-aspartato) en líquido cefalorraquídeo (LCR) por ensayo basado en células - cell bassed assay (CBA). Resultados: Reunieron criterios de EA probable 94 pacientes con una edad media de 89.5 meses, 51% mujeres. Se dividieron en dos grupos: seropositivos y seronegativos de acuerdo al resultado del biomarcador. Seropositivos 45/94. El síntoma inicial más frecuente fue: convulsiones. El 28% requirió ingreso a Unidad de Cuidados Intensivos (UCI). 4 pacientes seropositivos y 1 seronegativo tuvieron encefalitis por el virus del herpes simple (Om) previamente. En una paciente seronegativa se diagnosticó teratoma ovárico. Hallazgos de estudios complementarios: LCR patológico en el 29%, RM cerebral en el 52%, EEG en el 74%. El tratamiento de primera línea más empleado fue MP + IVIg. El 46% de los pacientes presentó recuperación completa. Entre los pacientes que recibieron RTX, el 65% tuvo una recuperación completa. Ningún paciente que recibió RTX presentó recaída. Conclusión: Ante la sospecha de EA se debe considerar el inicio temprano de inmunoterapia para favorecer la rápida recuperación funcional. Se recomienda el uso temprano de RTX en los casos con presentación grave o respuesta subóptima al tratamiento de primera línea para beneficiar la respuesta clínica y reducir el riesgo de recaída (AU)

Introduction: Encephalitis due to antibodies against the N-methyl-D-aspartate receptor (NMDA-R) is an inflammatory disorder of the central nervous system (CNS) in which autoantibodies directed against the NR1 subunit of the N-methyl-D-aspartate (NMDA) receptor develop a set of neuropsychiatric symptoms, seizures, and abnormal movements. The recommended treatment includes methylprednisolone (MP) and intravenous immunoglobulin (IVIg), and/or therapeutic plasma exchange (TPE); and in case of non-response: rituximab (RTX) and/or cyclophosphamide (CFM). Objectives: To analyze clinical, biochemical, electroencephalogram (EEG), magnetic resonance imaging (MRI) of the brain, treatments received, and outcomes observed in a series of patients with probable or confirmed autoimmune encephalitis (AE). Materials and methods: We analyzed the medical records of patients under 17 years of age who met Graus' diagnostic criteria (2016) for probable AE, with follow-up of more than 6 months, hospitalized at Hospital Garrahan between 2008 and 2023. Diagnosis was defined by the identification of anti-NMDAR antibodies (N-methyl D-aspartate) in cerebrospinal fluid (CSF) by cell-based assay (CBA). Results: Ninety-four patients met criteria for probable AE with a mean age of 89.5 months, 51% female. They were divided into two groups: seropositive and seronegative according to the biomarker result. Seropositive 45/94. The most frequent initial symptom was seizures. Twenty-eight percent required admission to the Intensive Care Unit (ICU). Four seropositive patients and one seronegative patient had previously had herpes simplex encephalitis (Om). Ovarian teratoma was diagnosed in one seronegative patient. Findings of complementary studies: Pathological CSF in 29%, brain MRI in 52%, EEG in 74%. The most commonly used first-line treatment was MP + IVIg. Forty-six percent of patients experienced complete recovery. Among patients who received RTX, 65% had complete recovery. No patient who received RTX experienced relapse. Conclusion: In the suspicion of AE, early initiation of immunotherapy should be considered to promote rapid functional recovery. Early use of RTX is recommended in cases with severe presentation or suboptimal response to first-line treatment to benefit clinical response and reduce the risk of relapse (AU)

A Cocktail of Natural Compounds Holds Promise for New Immunotherapeutic Potential in Head and Neck Cancer / 中国结合医学杂志

OBJECTIVE@#To obtain detailed understanding on the gene regulation of natural compounds in altering prognosis of head and neck squamous cell carcinomas (HNSC).@*METHODS@#Gene expression data of HNSC samples and peripheral blood mononuclear cells (PBMCs) of HNSC patients were collected from Gene Expression Omnibus (GEO). Differential gene expression analysis of GEO datasets were achieved by the GEO2R tool. Common differentially expressed gerres (DEGs) were screened by comparing DEGs of HNSC with those of PBMCs. The combination was further analyzed for regulating pathways and biological processes that were affected.@*RESULTS@#Totally 110 DEGs were retrieved and identified to be involved in biological processes related to tumor regulation. Then 102 natural compounds were screened for a combination such that the expression of all 110 commonly DEGs was altered. A combination of salidroside, ginsenoside Rd, oridonin, britanin, and scutellarein was chosen. A multifaceted, multi-dimensional tumor regression was showed by altering autophagy, apoptosis, inhibiting cell proliferation, angiogenesis, metastasis and inflammatory cytokines production.@*CONCLUSIONS@#This study has helped develop a unique combination of natural compounds that will markedly reduce the propensity of development of drug resistance in tumors and immune evasion by tumors. The result is crucial to developing a combinatorial natural therapeutic cocktail with accentuated immunotherapeutic potential.

Research Progress of Granulocytic Myeloid-derived Suppressor Cells in Non-small Cell Lung Cancer / 中国肺癌杂志

Granulocytic myeloid-derived suppressor cells (G-MDSCs) are one of the main subgroups of MDSCs, which are widely enriched in most cancers. It can inhibit the killing function of T-lymphocyte through the expression of arginase-1 (Arg-1) and reactive oxygen species (ROS), reshape the tumor immune microenvironment, and promote the occurrence and development of tumors. In recent years, more and more studies have found that G-MDSCs are significantly correlated with the prognosis and immunotherapy efficacy of patients with non-small cell lung cancer, and the use of drugs specifically targeting the recruitment, differentiation and function of G-MDSCs can effectively inhibit tumor progression. This article reviews the immunosuppressive effect of G-MDSCs in non-small cell lung cancer and the progress of related pathway targeting drugs.
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Progress of Immunotherapy in EGFR-mutated Advanced Non-small Cell Lung Cancer / 中国肺癌杂志

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently the first-line standard of care for patients with non-small cell lung cancer (NSCLC) that harbor EGFR mutations. Nevertheless, resistance to EGFR-TKIs is inevitable. In recent years, although immune checkpoint inhibitors (ICIs) have significantly shifted the treatment paradigm in advanced NSCLC without driver mutation, clinical benefits of these agents are limited in patients with EGFR-mutated NSCLC. Compared with wild-type tumors, tumors with EGFR mutations show more heterogeneity in the expression level of programmed cell death ligand 1 (PD-L1), tumor mutational burden (TMB), and other tumor microenvironment (TME) characteristics. Whether ICIs are suitable for NSCLC patients with EGFR mutations is still worth exploring. In this review, we summarized the clinical data with regard to the efficacy of ICIs in patients with EGFR-mutated NSCLC and deciphered the unique TME in EGFR-mutated NSCLC.
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Predictive Value of Peripheral Blood Biomarkers in the Treatment of Lung Cancer Patients with Anti PD-1 Immunotherapy / 中国肺癌杂志

BACKGROUND@#The application of programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) antibodies has greatly improved the clinical outcomes of lung cancer patients. Here, we retrospectively analyzed the efficacy of PD-1 antibody therapy in locally advanced non-surgical or metastatic lung cancer patients, and preliminarily explored the correlation between peripheral blood biomarkers and clinical responses.@*METHODS@#We conducted a single center study that included 61 IIIA-IV lung cancer patients who received PD-1 antibody treatment from March 2020 to December 2021, and collected the medical record data on PD-1 antibody first-line or second-line treatment. The levels of multiple Th1 and Th2 cytokines in the patient's peripheral blood serum, as well as the phenotype of peripheral blood T cells, were detected and analyzed.@*RESULTS@#All the patients completed at least 2 cycles of PD-1 monoclonal antibody treatment. Among them, 42 patients (68.9%) achieved partial response (PR); 7 patients (11.5%) had stable disease (SD); and 12 patients (19.7%) had progressive disease (PD). The levels of peripheral blood interferon gamma (IFN-γ) (P=0.023), tumor necrosis factor α (TNF-α) (P=0.007) and interleukin 5 (IL-5) (P=0.002) before treatment were higher in patients of the disease control rate (DCR) (PR+SD) group than in the PD group. In addition, the decrease in absolute peripheral blood lymphocyte count after PD-1 antibody treatment was associated with disease progression (P=0.023). Moreover, the levels of IL-5 (P=0.0027) and IL-10 (P=0.0208) in the blood serum after immunotherapy were significantly increased compared to baseline.@*CONCLUSIONS@#Peripheral blood serum IFN-γ, TNF-α and IL-5 in lung cancer patients have certain roles in predicting the clinical efficacy of anti-PD-1 therapy. The decrease in absolute peripheral blood lymphocyte count in lung cancer patients is related to disease progression, but large-scale prospective studies are needed to further elucidate the value of these biomarkers.

Research progress on immunotherapy based on NK cells for hepatocellular carcinoma / 细胞与分子免疫学杂志

Hepatocellular carcinoma (HCC) is well characterized as a heterogeneous disease. Its late-stage diagnosis and chemotherapy resistance make it one of the refractory tumors in China. Natural killer (NK) cells play a significant role in immune surveillance. However, NK cells become dysfunctional in the progression of HCC, leading to tumor immune escape. This article reviews the recent progress on different strategies of NK cell-based immunotherapy in treating HCC, including direct adoptive NK cell transfer, gene engineering in NK cell, NK cell receptor targeting, immunosuppressive microenvironment modification, and tumor toxicity enhancement by cytokines or traditional Chinese medicine. These NK cell-based strategies have shown promising therapeutic potential.

Progress in targeted inhibition of aerobic glycolysis combined with immunotherapy for renal cell carcinoma / 细胞与分子免疫学杂志

Tumor aerobic glycolysis is one of the main features of tumor metabolic reprogramming. This abnormal glycolytic metabolism provides bioenergy and biomaterials for tumor growth and proliferation. It is worth noting that aerobic glycolysis will not only provide biological materials and energy for tumor cells, but also help tumor cells to escape immune surveillance through regulation of immune microenvironment, thereby resisting tumor immunotherapy and promoting tumor progression. Based on the pathogenesis of renal cell carcinoma, this paper describes the characteristics of aerobic glycolysis, the effect of glycolytic metabolism on the immune microenvironment of renal cell carcinoma, the effect of glycolysis inhibitors on the immune microenvironment of renal cell carcinoma, and the prospect of glycolysis inhibitors combined with immune checkpoint inhibitors in the treatment of renal cell carcinoma.

γδ T cells: Major advances in basic and clinical research in tumor immunotherapy / 中华医学杂志(英文版)

γδ T cells are a kind of innate immune T cell. They have not attracted sufficient attention because they account for only a small proportion of all immune cells, and many basic factors related to these cells remain unclear. However, in recent years, with the rapid development of tumor immunotherapy, γδ T cells have attracted increasing attention because of their ability to exert cytotoxic effects on most tumor cells without major histocompatibility complex (MHC) restriction. An increasing number of basic studies have focused on the development, antigen recognition, activation, and antitumor immune response of γδ T cells. Additionally, γδ T cell-based immunotherapeutic strategies are being developed, and the number of clinical trials investigating such strategies is increasing. This review mainly summarizes the progress of basic research and the clinical application of γδ T cells in tumor immunotherapy to provide a theoretical basis for further the development of γδ T cell-based strategies in the future.

Development, Histological, and Ultrastructural Evaluation of Sheep Hyperimmune Serum Therapy for COVID-19 / Desarrollo, Evaluación Histológica y Ultraestructural de la Terapia con Suero Hiperinmune de Oveja para COVID-19

SUMMARY: In response to the threat posed by new variants of SARS-CoV-2 and the urgent need for effective treatments in the absence of vaccines, the aim of this study was to develop a rapid and cost-effective hyperimmune serum (HS) derived from sheep and assess its efficacy. The utilization of a halal-certified, easily maintained in certain geographic regions, easy-to-handle animal such as sheep could provide a viable alternative to the expensive option of horses. Sheep were immunized with a whole inactivated SARS-CoV- 2 antigen to produce HS, which was evaluated for neutralizing potency using the PRNT50 assay. K18-hACE2 transgenic mice (n=35) were divided into three groups: control, SARS-CoV-2 exposure through inhalation, and SARS-CoV-2 exposed mice treated with HS. HS efficacy was assessed through serum proinflammatory cytokine levels, qRT-PCR analysis, histopathological examination of lungs and hearts, and transmission electron microscopy. Purified HS exhibited significant neutralizing activity (1/24,576). The SARS-CoV-2+HS group showed lower levels of TNF-α, IL-10, and IL-6 (P<0.01) and relatively lower levels of MCP-1 compared to the SARS-CoV-2 group. HS prevented death, reduced viral RNA levels in the lungs and hearts, protected against severe interstitial pneumonia, preserved lung tissue integrity, and prevented myocyte damage, while the SARS-CoV-2 group exhibited viral presence in the lungs. This study successfully developed a sheep-derived HS against the entire SARS-CoV-2 virus, resulting in a significant reduction in infection severity, inflammation, and systemic cytokine production. The findings hold promise for treating severe COVID-19 cases, including emerging viral variants, and immunocompromised patients.

En respuesta a la amenaza que suponen las nuevas variantes del SARS-CoV-2 y la urgente necesidad de tratamientos eficaces en ausencia de vacunas, el objetivo de este estudio fue desarrollar un suero hiperinmune (HS) rápido y rentable derivado de ovejas. y evaluar su eficacia. La utilización de un animal con certificación halal, de fácil mantenimiento en determinadas regiones geográficas y de fácil manejo, como las ovejas, podría proporcionar una alternativa viable a la costosa opción de los caballos. Las ovejas fueron inmunizadas con un antígeno de SARS-CoV-2 completamente inactivado para producir HS, cuya potencia neutralizante se evaluó mediante el ensayo PRNT50. Los ratones transgénicos K18-hACE2 (n = 35) se dividieron en tres grupos: control, exposición al SARS-CoV-2 mediante inhalación y ratones expuestos al SARS-CoV-2 tratados con HS. La eficacia de HS se evaluó mediante niveles de citoquinas proinflamatorias en suero, análisis qRT-PCR, examen histopatológico de pulmones y corazones y microscopía electrónica de transmisión. El HS purificado exhibió una actividad neutralizante significativa (1/24,576). El grupo SARS-CoV-2+HS mostró niveles más bajos de TNF-α, IL-10 e IL-6 (P<0,01) y niveles relativamente más bajos de MCP-1 en comparación con el grupo SARS-CoV-2. HS evitó la muerte, redujo los niveles de ARN viral en los pulmones y el corazón, protegió contra la neumonía intersticial grave, preservó la integridad del tejido pulmonar y evitó el daño de los miocitos, mientras que el grupo SARS-CoV-2 exhibió presencia viral en los pulmones. Este estudio desarrolló con éxito un HS derivado de ovejas contra todo el virus SARS-CoV-2, lo que resultó en una reducción significativa de la gravedad de la infección, la inflamación y la producción sistémica de citocinas. Los hallazgos son prometedores para el tratamiento de casos graves de COVID- 19, incluidas las variantes virales emergentes y los pacientes inmunocomprometidos.

Diabetes mellitus tipo 1 de presentación súbita inducida por inhibidores del punto de control inmunitario en el tratamiento de cáncer avanzado. Serie de casos / Sudden onset type 1 diabetes mellitus induced by immune checkpoint inhibitors in the treatment of advanced cancer. Cases report

Tres pacientes con cáncer avanzado en tratamiento con inhibidores del punto de control inmunitario (inmune checkpoint inhibitors, ICIs), sin antecedentes de diabetes mellitus (DM), ingresaron al Servicio de Urgencias con poliuria, polidipsia y pérdida de peso, y diagnóstico de cetoacidosis diabética, sin evidencia clínica de infección. Fueron tratados con líquidos e infusión de insulina pasando luego a un régimen de insulina bolo basal que continuó después del alta. Las pruebas de detección de autoanticuerpos para DM resultaron negativas, y se les diagnosticó DM inducida por ICIs, pembrolizumab en dos de ellos y nivolumab en el otro. El propósito de esta serie de casos es demostrar el desarrollo de la DM1 en forma aguda en pacientes tratados con inhibidores de PD-1. Sobre la base de estos casos y la literatura revisada, se buscaron determinar las características clínicas, y sugerir estrategias para la identificación, control, tratamiento precoz y seguimiento de los pacientes tratados con ICIs a fin de minimizar el impacto de la disfunción autoinmune.

Three patients with advanced cancer, treated with inmune checkpoint inhibitors (ICIs), with no history of diabetes mellitus (DM), were admitted to the Emergency Department with polyuria, polydipsia, and weight loss and a diagnosis of diabetic ketoacidosis without clinical evidence of infection. They were treated with fluids and insulin infusion transitioning to a basal-bolus insulin regimen, which continued after discharge. Autoantibody detection tests for DM were negative and they were diagnosed with DM induced by ICIs, pembrolizumab in two of them, and nivolumab in another. The purpose of this case report is to show the development of DM1 in an acute form in patients treated with PD-1 inhibitors. Based on these cases and the reviewed literature, we seek to identify clinical characteristics and suggest strategies for the proper identification, control, treatment, and follow-up of patients treated with ICIs to minimize the impact of autoimmune dysfunction.

Inmunoterapia para el tratamiento del cáncer de cabeza y cuello ¿dónde estamos y hacia dónde vamos? / Immunotherapy for the treatment of head and neck cancer: where are we and where are we going?

El cáncer de cabeza y cuello comprende a todos aquellos tumores que se desarrollan en el tracto aerodigestivo superior, una de las características de éstos es su diversidad, que no es solo desde el punto de vista histológico y etiológico, sino que incluyen diversas formas de presentación, progresión y enfoques terapéuticos. Son de causa multifactorial, siendo el alcohol y el tabaco los principales factores de riesgo asociados; en los últimos años se ha relacionado a ciertos virus con potencial oncogénico con la génesis tumoral, entre ellos al Virus del Papiloma Humano, lo que ha permitido modificar el sistema de estadificación tumor primario-nodos linfáticos cancerosos-metástasis (TNM); presentándolo ahora en dos grandes grupos acorde a la Proteína supresora de tumores P16: P16+ y P16-,los cuales tienen características y manejo diferente. En vista de la heterogeneidad de la enfermedad, son diversos los tratamientos que se ha empleados para el manejo de la misma, entre ellos cirugía, radioterapia, quimioterapia e/o inmunoterapia; ésta última terapéutica, está dirigida hacia la estimulación del sistema inmune del paciente con la finalidad de generar la destrucción de las células tumorales, se realizan previo a una intervención quirúrgica para reducir el tamaño del tumor. Una forma destacable, es la del bloqueo de puntos de control inmunitarios, especialmente hacia proteínas de control inmune moduladoras de respuesta de células T, como los anti-PD-1 y los anti-CTLA-4. La inmunoterapia cada vez va tomando más protagonismo en oncología, en especial las formas de evasión de las reacciones inmunitarias por parte de las células cancerígenas(AU)

Head and neck cancer includes all those tumors that develop in the upper aerodigestive tract, one of the characteristics of these is their heterogeneity, which is not only from the histological and etiological, but also include various forms of presentation, progression and therapeutic approaches.They have a multifactorial cause, with alcohol and tobacco being the main associated risk factors, however, in recent year scertain viruses with oncogenic potential have been linked to tumor genesis, including HPV, which has made it possible tomodify the TNM staging system; now presenting it in two large groups, P16+ and P16-, which have different characteristics and management. In view of the heterogeneity of the disease, there are various treatments that have been used to manageit, including surgery, radiotherapy, chemotherapy and/ orimmunotherapy which will be determined taking into account the location and tumor extension. The latter treatment, is aimedat stimulating the patient's immune system in order to generate the destruction of tumor cells, are performed prior to a surgical intervention to reduce the size of the tumor. A remarkable therapy is that of blocking immune checkpoints, especially anti-PD-1 and anti-CTLA. Immunotherapy is becoming more and more prominent, however, there is still much to discover, so we believe that we should continue investigating the ways of evasion of immune reactions by cancer cells(AU)

Cetoacidosis diabética como debut de diabetes mellitus inmunomediada en paciente en tratamiento con inhibidores de checkpoint / Diabetic ketoacidosis as debut of immune-mediated diabetes mellitus in a patient in treatment with immune checkpoint inhibitors

Los inhibidores de checkpoint (ICP) son anticuerpos usados en inmunoterapia contra el cáncer. Uno de sus blancos de acción es el receptor de muerte celular programada-1 (PD-1), el cual es importante para mantener la tolerancia inmunitaria. Sin embargo, este mecanismo se asocia a riesgo de eventos adversos relacionados a la inmunidad que pueden afectar a múltiples órganos incluyendo el sistema endocrino. Se describe el caso inhabitual de un paciente que a los 18 meses de terapia con ICP debutó con cetoacidosis diabética (CAD).

Immune checkpoint inhibitors consist in antibodies used in immunotherapy against cancer. One of their targets is the programmed cell death-1 (PD-1) receptor, which is important in maintaining self-tolerance. However, this mechanism is associated with a risk for immune-related adverse events potentially affecting multiple organs, including the endocrine system. We describe the unusual case of a patient who, after 18 months of treatment with an immune checkpoint inhibitor, debuted with diabetic ketoacidosis

Supervivencia extendida con pembrolizumab en un paciente con cáncer de pulmón no microcítico estadio IV: Reporte de caso / Extendedsurvival with pembrolizumab in a patient with stage IV non-small cell lung cancer:A case report

Introducción:La inmunoterapia con pembrolizumab ha mejorado el pronóstico del cáncer de pulmón metastásico. En el presente caso se presenta la supervivencia extendidad y evolución de un paciente específico.Caso clínico:Hombre de 66 años, fumador. Diagnosticado de masa pulmonar en lóbulo infe-rior izquierdo de dimensiones 9 x 8 cm, con metástasis supra e infratentoriales intraaxiliares. Taller diagnóstico: Establecida como neoplasia de pulmón en estadio IVc, se comprobó el estado de PDL1 que positivo en un 80 % de la muestra de masa pulmonar. Debuta con me-tástasis cerebrales.Evolución: Se inció inmunoterapia con Pembrolizumab, el cual se mantubo hasta la presencia de un efecto secundario atribuido al pembrolizumab, cumpliendo 30meses de supervivencia hasta el cierre de esta observación no se reportó la muerte del paciente.Conclusiones:En el presente reporte, la determinación del biomarcador histológico PDL1 po-sitivo en cáncer de pulmón ayudo a prescribir un tratamiento con inmunoterpia dirigida, lo que demostró aumentar la supervivencia más allá que el tratamiento convencional con quimiote-rapia

Introduction: Immunotherapy with pembrolizumab has improved the prognosis of metastatic lung cancer. A specific patient's extended survival and evolution is presented in the present case.Clinical case: 66-year-old man, smoker. Diagnosed with a lung mass in the left lower lobe measuring 9 x 8 cm, with supra and infratentorial intra-axial metastases.Diagnostic workshop: To establisha stage IVc lung neoplasm, 80% of the lung mass sample was confirmed to be positive for PDL1.Evolution: Immunotherapy was started with Pembrolizumab, which was maintained until the presence of a side effect attributed to pembrolizumab, completing 30 months of survival until the closure of this observation, the patient's death was not reported.Conclusions: In the present report, the determination of the positive histological biomarker PDL1 in lung cancer helped prescribe treatment with targeted immunotherapy, which was shown to increase survival beyond conventional treatment with chemotherapy

STIP1 correlates with tumor immune infiltration and prognosis as a potential immunotherapy target: a pan-cancer bioinformatics analysis / 南方医科大学学报

OBJECTIVE@#To investigate the correlation of stress-inducible phosphoprotein 1 (STIP1) expression level with prognosis of different cancers and its potential role in immunotherapy.@*METHODS@#TCGA, TARGET and GTEx databases were used for bioinformatic analysis of STIP1 expression level and its prognostic value in different cancers. We also detected STIP1 expression immunohistochemically in 10 pairs of colorectal cancer and adjacent tissues. We further analyzed the correlation of STIP1 expression level with tumor mutational burden, microsatellite instability, immune cell infiltration, immune regulators and outcomes of different cancers. STIP1- related proteins were identified using protein- protein interaction (PPI) network analysis, and functional enrichment analysis was performed to analyze the regulatory pathways involving STIP1.@*RESULTS@#Bioinformatics analysis showed that STIP1 was highly expressed in most tumors compared with the normal tissues (P < 0.05), which was confirmed by immunohistochemistry of the 10 pairs of colorectal cancer tissues. STIP1 expression level was correlated with clinical stages of multiple cancers (P < 0.05), and in some cancer types, an upregulated STIP1 expression was correlated with a poor prognosis of the patients in terms of overall survival, disease-specific survival, disease-free survival and progression-free survival (P < 0.05). STIP1 expression was significantly correlated with tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors in most tumors (P < 0.05). PPI network analysis indicated that STIP1-related proteins included HSPA4, HSPA8, and HSP90AA1. KEGG enrichment analysis suggested that the high expression of STIP1 in liver cancer was related mainly with valerate metabolism, tryptophan metabolism, and butyrate metabolism pathways; HALLMARK enrichment analysis suggested high STIP1 expression in liver cancer was involved in bile acid and fatty acid metabolism.@*CONCLUSION@#STIP1 is up-regulated in multiple cancer types and its expression level is correlated with clinical tumor stage, tumor mutational burden, microsatellite instability, immune cell infiltration and immunomodulatory factors.

Application of Neoadjuvant Chemoimmunotherapy in Resectable NSCLC / 中国肺癌杂志

BACKGROUND@#For resectable non-small cell lung cancer (NSCLC), the CheckMate-816 study demonstrated that neoadjuvant chemoimmunotherapy increased the rate of complete pathologic response (pCR) by 21.8% compared with chemotherapy alone and resulted in a significant benefit in event-free survival (EFS). This study aimed to investigate the safety and feasibility of this approach in the real world.@*METHODS@#Clinical data from patients with NSCLC who underwent surgery after neoadjuvant chemoimmunotherapy or chemotherapy alone in two centers were analyzed retrospectively, and subgroup analyses were performed for the chemoimmunotherapy group according to treatment cycle. The primary study endpoints were EFS and major pathologic response (MPR), and the secondary study endpoints were pCR, overall survival (OS), treatment-related adverse events (TRAEs), and surgery-related metrics.@*RESULTS@#As of April 2023, 89 patients had been enrolled, including 54 in the chemoimmunotherapy group and 35 in the chemotherapy alone group. MPR was achieved in 31 (57.4%) and 5 (14.3%) patients in the chemoimmunotherapy group and chemotherapy alone group, respectively (OR=8.09, 95%CI: 2.72-24.04, P<0.001); pCR was achieved in 25 (46.3%) patients in the chemoimmunotherapy group and no patient in the chemotherapy alone group (P<0.001). The median follow-up time was 22.1 months. At 24 months, the EFS rates of the chemoimmunotherapy group and the chemotherapy alone group were 77.0% and 56.7%, respectively (P=0.026), and the OS rates were 87.1% and 67.7%, respectively (P=0.020). In the neoadjuvant chemoimmunotherapy group, there was no significant difference between the 1-2 cycles and 3-5 cycles groups in terms of operation time, intraoperative blood loss, and postoperative complications.@*CONCLUSIONS@#Neoadjuvant chemoimmunotherapy was more effective than chemotherapy alone and did not increase the risk associated with surgery. An increase in the number of cycles of neoadjuvant chemoimmunotherapy had no significant effect on the difficulty of surgery.

Advances in Predictive Research of Immune Checkpoint Inhibitors-related Adverse Events / 中国肺癌杂志

The era of tumor treatment has been revolutionized by the advent of immune checkpoint inhibitors. However, while immunotherapy benefits patients, it can also lead to immune-related adverse events that may affect multiple organs and systems throughout the body, potentially even posing a life-threatening risk. The diverse clinical manifestations and onset times of these adverse events further complicate their prediction and diagnosis. The purpose of this paper is to review the clinical characteristics and predicted biomarkers of adverse events related to inhibitors at immune checkpoints, in order to help clinicians evaluate drug risks and early warn adverse events.
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Research Progress of Lung Cancer Vaccines / 中国肺癌杂志

With the development of medical technology, tumor vaccines as a novel precise immunotherapy approach have gradually received attention in clinical applications. Against the backdrop of the global corona virus disease 2019 (COVID-19) outbreak, vaccine technology has further advanced. Depending on the types of antigens, tumor vaccines can be divided into whole-cell vaccines, peptide vaccines, messenger ribonucleic acid (mRNA) vaccines, recombinant virus vaccines, etc. Although some tumor vaccines have been marketed and achieved certain therapeutic effects, the results of tumor vaccines in clinical trials have been unsatisfactory in the past period. With the maturation of next-generation sequencing (NGS) technology and the continuous development of bioinformatics, dynamic monitoring of the entire process of tumor subpopulation development has become a reality, which has laid a solid foundation for personalized, neoantigen-centered therapeutic tumor vaccines. This article reviews the recent developments of tumor vaccines of different types, starts with lung cancer and summarizes the achievements of tumor vaccines in clinical applications, and provides an outlook for the future development of antigen-centered tumor vaccines.
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Progress in Image-planned and Real-time Image-guided Lung Cancer Biopsy in the Detection of Biomarkers / 中国肺癌杂志

With the progress of targeted therapy and immunotherapy for lung cancer, the clinical demand for lung biopsy is increasing. An ideal biopsy specimen can be used not only for histopathological diagnosis, but also for biomarker detection. The ideal biopsy specimen should meet two requirements, including more than 60 mm2 of tumor tissue and containing more than 20% of tumor cells. In order to obtain ideal lung cancer biopsy specimens, advanced imaging techniques are needed to help. In this article, we reviewed the requirements for biopsy specimens based on biomarker detection, as well as the current status and research progress of using imaging techniques for preoperative planning and intraoperative real time guidance of lung cancer biopsy.
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Recent Progress of Tertiary Lymphoid Structure in Prognosis and Immunotherapy of Non-small Cell Lung Cancer / 中国肺癌杂志

Lung cancer is the leading cause of cancer death, and non-small cell lung cancer (NSCLC) accounts for 85%. Immunotherapy has significantly improved the clinical prognosis of patients with NSCLC. However, because of the complexity and heterogeneousness of the tumor microenvironment, only a subset of individuals can benefit from immunotherapy. Therefore, it is necessary to explore effective predictive biomarkers for immunotherapy of NSCLC. Tertiary lymphoid structure (TLS) is an ectopic lymphoid organ that is highly similar to secondary lymphoid organs (SLO), and the presence of TLS has been found to be closely associated with a good prognosis in immunotherapy for a variety of solid tumors, including NSCLC. This article provides a review of the prognostic role of tertiary lymphoid structures in immunotherapy of NSCLC, in order to offer references for screening suitable candidates for immunotherapy of NSCLC and develop personalized and precise treatment plans.
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