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1.
Immunity ; 54(9): 2117-2132.e7, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34525340

RESUMO

The nature of the anti-tumor immune response changes as primary tumors progress and metastasize. We investigated the role of resident memory (Trm) and circulating memory (Tcirm) cells in anti-tumor responses at metastatic locations using a mouse model of melanoma-associated vitiligo. We found that the transcriptional characteristics of tumor-specific CD8+ T cells were defined by the tissue of occupancy. Parabiosis revealed that tumor-specific Trm and Tcirm compartments persisted throughout visceral organs, but Trm cells dominated lymph nodes (LNs). Single-cell RNA-sequencing profiles of Trm cells in LN and skin were distinct, and T cell clonotypes that occupied both tissues were overwhelmingly maintained as Trm in LNs. Whereas Tcirm cells prevented melanoma growth in the lungs, Trm afforded long-lived protection against melanoma seeding in LNs. Expanded Trm populations were also present in melanoma-involved LNs from patients, and their transcriptional signature predicted better survival. Thus, tumor-specific Trm cells persist in LNs, restricting metastatic cancer.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Memória Imunológica/imunologia , Linfonodos/imunologia , Melanoma Experimental/imunologia , Melanoma/imunologia , Neoplasias Cutâneas/imunologia , Animais , Humanos , Camundongos , Vitiligo , Melanoma Maligno Cutâneo
2.
J Surg Res ; 300: 345-351, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38843721

RESUMO

INTRODUCTION: Food desert (FD) residence has emerged as a risk factor for poor outcomes in breast, colon and esophageal cancers. The purpose of this retrospective study was to examine FD residence as an associated risk factor in nonsmall cell lung cancer (NSCLC) patients treated with anatomic lung resection (ALR). METHODS: All consecutive ALRs for stage I-III NSCLC from January 2015 to December 2017 at a single institution were reviewed. The primary exposure of interest was FD residence as defined by the United States Department of Agriculture. The primary outcome was 5-y overall mortality. Secondary outcomes were 30-d complications and 1- and 3-y mortality. Cox proportional hazard analysis was used to model factors associated with each outcome, adjusted for covariates. RESULTS: A total of 348 ALRs were included, with 101 (29%) patients residing in an FD. In the unadjusted Cox model, those residing in FD had an associated lower 5-year mortality risk compared to those not residing in an FD (hazard ratio = 0.56, 95% confidence interval (0.33-0.97); P = 0.04). That association was not statistically significant once adjusted for covariates (hazard ratio = 0.59, 95% confidence interval (0.34-1.04); P = 0.07). CONCLUSIONS: In this study, FD residence was not associated with an increase in the risk of 5-y mortality. Selection bias of patients deemed healthy enough to undergo surgery may have mitigated the negative association of FD residence demonstrated in other cancers. Future work will evaluate all NSCLC patients undergoing treatments at our institution to further evaluate FDs as a risk factor for worse outcomes.

3.
Pediatr Int ; 65(1): e15525, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36905298

RESUMO

BACKGROUND: The coronavirus disease 2019 outbreak has prompted some hospitals to implement screening tests upon admission since 2020. FilmArray® Respiratory 2.1 Panel (FilmArray) is a multiplex polymerase chain reaction (PCR) test with high sensitivity and specificity for detecting respiratory pathogens. We aimed to assess the clinical influence of the routine use of FilmArray for pediatric patients, including those without symptoms suggestive of an infection. METHODS: We conducted a single-center retrospective observational study, which investigated patients aged ≤15 years who underwent FilmArray on admission in 2021. We collected the patients' epidemiological information, symptoms, and FilmArray results from their electronic health records. RESULTS: A positive result was observed in 58.6% of patients admitted to the general ward or intensive care unit (ICU) but only in 1.5% of patients in the neonatal ward. Among the patients admitted to the general ward or ICU who tested positive, 93.3% had symptoms suggestive of infections, 44.6% had a sick contact before admission, and 70.5% had siblings. However, 62 (28.2%) out of 220 patients without the four (fever, respiratory, gastrointestinal, and dermal) symptoms also had positive results. Among them, 18 patients with adenovirus and three with respiratory syncytial virus were isolated to private rooms. However, 12 (57.1%) patients were discharged without symptoms suggestive of viral infection. CONCLUSION: Multiplex PCR routine use for all inpatients may lead to excessive management of positive cases because FilmArray cannot quantify microorganisms. Thus, targets for testing should be considered carefully based on patients' symptoms and histories of sick contacts.


Assuntos
COVID-19 , Vírus Sincicial Respiratório Humano , Infecções Respiratórias , Viroses , Recém-Nascido , Humanos , Criança , Reação em Cadeia da Polimerase Multiplex/métodos , Infecções Respiratórias/diagnóstico , COVID-19/diagnóstico , COVID-19/epidemiologia , Teste para COVID-19
4.
Kidney Int ; 100(1): 196-205, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33359528

RESUMO

Immune checkpoint inhibitors (ICIs) are widely used for various malignancies. However, their safety and efficacy in patients with a kidney transplant have not been defined. To delineate this, we conducted a multicenter retrospective study of 69 patients with a kidney transplant receiving ICIs between January 2010 and May 2020. For safety, we assessed the incidence, timing, and risk factors of acute graft rejection. For efficacy, objective response rate and overall survival were assessed in cutaneous squamous cell carcinoma and melanoma, the most common cancers in our cohort, and compared with stage-matched 23 patients with squamous cell carcinoma and 14 with melanoma with a kidney transplant not receiving ICIs. Following ICI treatment, 29 out of 69 (42%) patients developed acute rejection, 19 of whom lost their allograft, compared with an acute rejection rate of 5.4% in the non-ICI cohort. Median time from ICI initiation to rejection was 24 days. Factors associated with a lower risk of rejection were mTOR inhibitor use (odds ratio 0.26; 95% confidence interval, 0.09-0.72) and triple-agent immunosuppression (0.67, 0.48-0.92). The objective response ratio was 36.4% and 40% in the squamous cell carcinoma and melanoma subgroups, respectively. In the squamous cell carcinoma subgroup, overall survival was significantly longer in patients treated with ICIs (median overall survival 19.8 months vs. 10.6 months), whereas in the melanoma subgroup, overall survival did not differ between groups. Thus, ICIs were associated with a high risk of rejection in patients with kidney transplants but may lead to improved cancer outcomes. Prospective studies are needed to determine optimal immunosuppression strategies to improve patient outcomes.


Assuntos
Carcinoma de Células Escamosas , Transplante de Rim , Neoplasias Cutâneas , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Inibidores de Checkpoint Imunológico , Transplante de Rim/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico
6.
Cancer Immunol Immunother ; 67(2): 311-325, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29052782

RESUMO

Malignant melanoma incidence has been increasing for over 30 years, and despite promising new therapies, metastatic disease remains difficult to treat. We describe preliminary results from a Phase I clinical trial (NCT01586403) of adoptive cell therapy in which three patients received autologous CD4+ and CD8+ T cells transduced with a lentivirus carrying a tyrosinase-specific TCR and a marker protein, truncated CD34 (CD34t). This unusual MHC Class I-restricted TCR produces functional responses in both CD4+ and CD8+ T cells. Parameters monitored on transduced T cells included activation (CD25, CD69), inhibitory (PD-1, TIM-3, CTLA-4), costimulatory (OX40), and memory (CCR7) markers. For the clinical trial, T cells were activated, transduced, selected for CD34t+ cells, then re-activated, and expanded in IL-2 and IL-15. After lymphodepleting chemotherapy, patients were given transduced T cells and IL-2, and were followed for clinical and biological responses. Transduced T cells were detected in the circulation of three treated patients for the duration of observation (42, 523, and 255 days). Patient 1 tolerated the infusion well but died from progressive disease after 6 weeks. Patient 2 had a partial response by RECIST criteria then progressed. After progressing, Patient 2 was given high-dose IL-2 and subsequently achieved complete remission, coinciding with the development of vitiligo. Patient 3 had a mixed response that did not meet RECIST criteria for a clinical response and developed vitiligo. In two of these three patients, adoptive transfer of tyrosinase-reactive TCR-transduced T cells into metastatic melanoma patients had clinical and/or biological activity without serious adverse events.


Assuntos
Antígenos de Neoplasias/imunologia , Melanoma/terapia , Receptores de Antígenos de Linfócitos T/imunologia , Neoplasias Cutâneas/terapia , Subpopulações de Linfócitos T/transplante , Adulto , Idoso , Humanos , Masculino , Melanoma/imunologia , Melanoma/patologia , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Neoplasias Cutâneas/imunologia , Neoplasias Cutâneas/secundário , Subpopulações de Linfócitos T/imunologia , Transplante Autólogo
7.
J Psychosoc Oncol ; 35(6): 646-665, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28459393

RESUMO

The purpose of this study was to examine the physical and emotional well-being and social support in newly diagnosed head and neck cancer (HNC) patients and caregivers and identify sociodemographic, clinical, and behavioral risk factors associated with compromised well-being in patients and caregivers. Newly diagnosed HNC patients and their primary caregivers (N = 72 dyads) completed questionnaires before treatment assessing physical and mental well-being, depression, cancer worry, and open-ended support questions. Patients reported worse physical well-being than caregivers (p < 0.05) but similar levels of mental well-being. Caregivers reported providing emotional and instrumental support most frequently with an emphasis on nutrition and assistance with speech, appearance, and addictions. Both patients and their caregivers reported suboptimal mental well-being and depression. Smoking was associated with compromised well-being in patients, caregivers, and dyads. Compromised well-being in patients and their caregivers was more likely when patients were younger, had worse symptoms, and smoked/consumed alcohol (p < 0.05). While patients face more physical strain than caregivers, both equally confront emotional challenges. Results highlight risk factors for compromised well-being in both patients and their caregivers that should be assessed at diagnosis to guide identification of needed dyadic-focused supportive care resources.


Assuntos
Cuidadores/psicologia , Neoplasias de Cabeça e Pescoço/psicologia , Nível de Saúde , Relações Interpessoais , Apoio Social , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidadores/estatística & dados numéricos , Feminino , Neoplasias de Cabeça e Pescoço/diagnóstico , Neoplasias de Cabeça e Pescoço/terapia , Humanos , Masculino , Transtornos Mentais/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco
8.
Adv Exp Med Biol ; 893: 179-187, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26667344

RESUMO

Chromosomal rearrangement in the anaplastic lymphoma kinase (ALK) gene was identified as an oncogenic driver in non-small cell lung cancer (NSCLC) in 2007. A multi-targeted ALK/ROS1/MET inhibitor, crizotinib, targeting this activated tyrosine kinase has led to significant clinical benefit including tumor shrinkage and prolonged survival without disease progression and has been approved by US FDA since 2011 for the treatment of advanced ALK-rearranged NSCLC (Ou et al. Oncologist 17:1351-1375, 2012). Knowledge gained from treating ALK-rearranged NSCLC patients including the presenting clinicopathologic characteristics, methods of detecting ALK-rearranged NSCLC, pattern of relapse and acquired resistance mechanisms while on crizotinib, and the clinical activities of more potent ALK inhibitors has led us to a detailed and ever expanding knowledge of the ALK signaling pathway in lung cancer but also raising many more questions that remained to be answered in the future. This book chapter will provide a concise summary of the importance of ALK signaling pathway in lung cancer. Understanding the ALK signaling pathway in lung cancer will likely provide the roadmap to the management of major epithelial malignancies driven by receptor tyrosine kinase rearrangement.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Receptores Proteína Tirosina Quinases/fisiologia , Transdução de Sinais/fisiologia , Quinase do Linfoma Anaplásico , Rearranjo Gênico , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Receptores Proteína Tirosina Quinases/antagonistas & inibidores , Receptores Proteína Tirosina Quinases/genética
9.
JAMA ; 311(19): 1998-2006, 2014 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-24846037

RESUMO

IMPORTANCE: Targeting oncogenic drivers (genomic alterations critical to cancer development and maintenance) has transformed the care of patients with lung adenocarcinomas. The Lung Cancer Mutation Consortium was formed to perform multiplexed assays testing adenocarcinomas of the lung for drivers in 10 genes to enable clinicians to select targeted treatments and enroll patients into clinical trials. OBJECTIVES: To determine the frequency of oncogenic drivers in patients with lung adenocarcinomas and to use the data to select treatments targeting the identified driver(s) and measure survival. DESIGN, SETTING, AND PARTICIPANTS: From 2009 through 2012, 14 sites in the United States enrolled patients with metastatic lung adenocarcinomas and a performance status of 0 through 2 and tested their tumors for 10 drivers. Information was collected on patients, therapies, and survival. INTERVENTIONS: Tumors were tested for 10 oncogenic drivers, and results were used to select matched targeted therapies. MAIN OUTCOMES AND MEASURES: Determination of the frequency of oncogenic drivers, the proportion of patients treated with genotype-directed therapy, and survival. RESULTS: From 2009 through 2012, tumors from 1007 patients were tested for at least 1 gene and 733 for 10 genes (patients with full genotyping). An oncogenic driver was found in 466 of 733 patients (64%). Among these 733 tumors, 182 tumors (25%) had the KRAS driver; sensitizing EGFR, 122 (17%); ALK rearrangements, 57 (8%); other EGFR, 29 (4%); 2 or more genes, 24 (3%); ERBB2 (formerly HER2), 19 (3%); BRAF, 16 (2%); PIK3CA, 6 (<1%); MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0. Results were used to select a targeted therapy or trial in 275 of 1007 patients (28%). The median survival was 3.5 years (interquartile range [IQR], 1.96-7.70) for the 260 patients with an oncogenic driver and genotype-directed therapy compared with 2.4 years (IQR, 0.88-6.20) for the 318 patients with any oncogenic driver(s) who did not receive genotype-directed therapy (propensity score-adjusted hazard ratio, 0.69 [95% CI, 0.53-0.9], P = .006). CONCLUSIONS AND RELEVANCE: Actionable drivers were detected in 64% of lung adenocarcinomas. Multiplexed testing aided physicians in selecting therapies. Although individuals with drivers receiving a matched targeted agent lived longer, randomized trials are required to determine if targeting therapy based on oncogenic drivers improves survival. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01014286.


Assuntos
Adenocarcinoma/genética , Genótipo , Neoplasias Pulmonares/genética , Terapia de Alvo Molecular , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma de Pulmão , Idoso , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Proto-Oncogenes , Análise de Sequência de DNA/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Análise de Sobrevida
10.
Melanoma Res ; 34(1): 70-75, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-37830935

RESUMO

Pembrolizumab and ipilimumab/nivolumab (ipi/nivo) combination are FDA-approved immune checkpoint inhibitor (ICI) therapies for metastatic melanoma. ICIs could result in various inflammation responses known as immune-related adverse events (IRAEs). We report a patient with metastatic melanoma who developed multiple IRAEs including sarcoidosis-like reaction (SLR), diabetic ketoacidosis (DKA), and worsening hypothyroidism on ICIs. A 71-year-old man with stage IIIC melanoma and lymph node metastasis began adjuvant therapy with pembrolizumab in May 2021. A surveillance positron emission tomography-computed tomography (PET-CT) scan four months later showed diffuse nodal uptake indicating potential metastases although the patient remained asymptomatic. His treatment was temporarily switched to ipi/nivo before biopsy was obtained for definitive diagnosis, which revealed non-caseating granulomas consistent with SLR. After resuming pembrolizumab, he developed DKA and worsening hypothyroidism in November 2021, both of which were attributed to IRAEs. His surveillance PET scan in March 2022 again revealed new hypermetabolic activity in several bones, subcutaneous tissue, and the left inguinal lymph node. Left inguinal node biopsy showed disease recurrence, while biopsies of hypermetabolic subcutaneous nodules and bone demonstrated non-caseating granulomas. Our case described a patient on ICIs who developed several IRAEs. SLR is often asymptomatic but remains a diagnostic challenge due to its indistinguishable appearance on imaging studies compared to metastasis. Better understanding of IRAEs and improved surveillance strategies are needed for optimal patient outcomes.


Assuntos
Antineoplásicos Imunológicos , Hipotireoidismo , Melanoma , Sarcoidose , Neoplasias Cutâneas , Masculino , Humanos , Idoso , Melanoma/patologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Cutâneas/patologia , Nivolumabe/efeitos adversos , Ipilimumab/efeitos adversos , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Antineoplásicos Imunológicos/efeitos adversos , Recidiva Local de Neoplasia , Sarcoidose/induzido quimicamente , Granuloma/induzido quimicamente , Hipotireoidismo/induzido quimicamente
11.
Nutrients ; 16(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38892554

RESUMO

This study examined whey protein's impact on insulin resistance in a high-fat diet-induced pediatric obesity mouse model. Pregnant mice were fed high-fat diets, and male pups continued this diet until 8 weeks old, then were split into high-fat, whey, and casein diet groups. At 12 weeks old, their body weight, fasting blood glucose (FBG), blood insulin level (IRI), homeostatic model assessment for insulin resistance (HOMA-IR), liver lipid metabolism gene expression, and liver metabolites were compared. The whey group showed significantly lower body weight than the casein group at 12 weeks old (p = 0.034). FBG was lower in the whey group compared to the high-fat diet group (p < 0.01) and casein group (p = 0.058); IRI and HOMA-IR were reduced in the whey group compared to the casein group (p = 0.02, p < 0.01, p < 0.01, respectively). The levels of peroxisome proliferator-activated receptor α and hormone-sensitive lipase were upregulated in the whey group compared to the casein group (p < 0.01, p = 0.03). Metabolomic analysis revealed that the levels of taurine and glycine, both known for their anti-inflammatory and antioxidant properties, were upregulated in the whey group in the liver tissue (p < 0.01, p < 0.01). The intake of whey protein was found to improve insulin resistance in a high-fat diet-induced pediatric obesity mouse model.


Assuntos
Dieta Hiperlipídica , Modelos Animais de Doenças , Resistência à Insulina , Fígado , Obesidade Infantil , Proteínas do Soro do Leite , Animais , Proteínas do Soro do Leite/farmacologia , Dieta Hiperlipídica/efeitos adversos , Masculino , Camundongos , Obesidade Infantil/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Feminino , Glicemia/metabolismo , Insulina/sangue , Metabolismo dos Lipídeos/efeitos dos fármacos , Gravidez , Camundongos Endogâmicos C57BL
12.
Epigenomics ; : 1-9, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38869472

RESUMO

Aim: This study addresses the challenge of predicting the response of head and neck squamous cell carcinoma (HNSCC) patients to immunotherapy. Methods: Using DNA methylation cytometry, we analyzed the immune profiles of six HNSCC patients who showed a positive response to immunotherapy over a year without disease progression. Results: There was an initial increase in CD8 T memory cells and natural killer cells during the first four cycles of immunotherapy, which then returned to baseline levels after a year. Baseline CD8 T cell levels were lower in HNSCC immunotherapy responders but became similar to those in healthy subjects after immunotherapy. Conclusion: These findings suggest that monitoring fluctuations in immune profiles could potentially identify biomarkers for immunotherapy response in HNSCC patients.


[Box: see text].

13.
bioRxiv ; 2024 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-38559200

RESUMO

The ecto-ATPase CD39 is expressed on exhausted CD8+ T cells in chronic viral infection and has been proposed as a marker of tumor-specific CD8+ T cells in cancer, but the role of CD39 in an effector and memory T cell response has not been clearly defined. We report that CD39 is expressed on antigen-specific CD8+ short-lived effector cells (SLECs), while it's co-ecto-enzyme, CD73, is found on memory precursor effector cells (MPEC) in vivo . Inhibition of CD39 enzymatic activity during in vitro T cell priming enhances MPEC differentiation in vivo after transfer and infection. The enriched MPEC phenotype is associated with enhanced tissue resident memory (T RM ) establishment in the brain and salivary gland following an acute intranasal viral infection, suggesting that CD39 ATPase activity plays a role in memory CD8+ T cell differentiation. We also show that CD39 is expressed on human and murine T RM across several non-lymphoid tissues and melanoma, while CD73 is expressed on both circulating and resident memory subsets in mice. In contrast to exhausted CD39+ T cells in chronic infection, CD39+ T RM are fully functional when stimulated ex vivo with cognate antigen. This work further expands the identity of CD39 beyond a T cell exhaustion marker.

15.
Am J Hematol ; 88(11): E265-72, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23828274

RESUMO

Hemophagocytic lymphohistiocytosis (HLH) is a rare systemic inflammatory syndrome that results from unrestrained immune cell activation. Despite significant advances in the understanding of the pathophysiology of HLH, interventions remain limited for this often-fatal condition. Secretory sphingomyelinase (S-SMase) is a pro-inflammatory lipid hydrolase that is upregulated in several inflammatory conditions, including HLH. S-SMase promotes the formation of ceramide, a bioactive lipid implicated in several human disease states. However, the role of the S-SMase/ceramide pathway in HLH remains unexplored. To further evaluate the role of S-SMase upregulation in HLH, we tested the serum of patients with HLH (n = 16; primary = 3, secondary = 13) and healthy control patients (n = 25) for serum S-SMase activity with tandem sphingolipid metabolomic profiling. Patients with HLH exhibited elevated levels of serum S-SMase activity, with concomitant elevations in several ceramide species and sphingosine, while levels of sphingosine-1-phosphate were significantly decreased. Importantly, the ratio of C16 -ceramide:sphingosine was uniquely elevated in HLH patients that died despite appropriate treatment, but remained low in HLH patients that survived, suggesting that this ratio may be of prognostic significance. Together, these results demonstrate upregulation of the S-SMase/ceramide pathway in HLH, and suggest that the balance of ceramide and sphingosine determine clinical outcomes in HLH. .


Assuntos
Linfo-Histiocitose Hemofagocítica/sangue , Esfingolipídeos/sangue , Esfingomielina Fosfodiesterase/sangue , Regulação para Cima , Adulto , Idoso , Biomarcadores/sangue , Ceramidas/sangue , Ceramidas/metabolismo , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Linfo-Histiocitose Hemofagocítica/diagnóstico , Linfo-Histiocitose Hemofagocítica/imunologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Esfingolipídeos/metabolismo , Esfingomielina Fosfodiesterase/metabolismo , Esfingosina/sangue , Esfingosina/metabolismo , Adulto Jovem
16.
Transpl Immunol ; 81: 101932, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37734447

RESUMO

BACKGROUND: The usage of immunotherapy to treat skin malignancies in transplant patients requires weighing the risk of acute organ transplant rejection with the potential reduction of antitumor efficacy by transplant immunosuppression. Reducing the duration of immune checkpoint inhibitor treatment may help prevent acute transplant rejection and late immune-related adverse events. CASE PRESENTATION: An allogenic kidney transplant patient who developed regionally metastatic cutaneous squamous cell carcinoma received four cycles of pembrolizumab with complete response to therapy. Therapy was discontinued due to fatigue, significant cancer response, and to reduce the risk of acute graft rejection. His renal function remained stable, and he achieved subsequent durable response after treatment discontinuation. CONCLUSION: Organ transplant recipients with complete response to immunotherapy for cutaneous squamous cell carcinoma may continue to respond despite early treatment cessation. This may reduce the risks of late immune-related adverse events and acute graft rejection.


Assuntos
Carcinoma de Células Escamosas , Transplante de Rim , Neoplasias Cutâneas , Masculino , Humanos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/etiologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/etiologia , Transplante de Rim/efeitos adversos , Rejeição de Enxerto , Imunoterapia
17.
BMJ Case Rep ; 16(7)2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37451798

RESUMO

The anti-PD-1 antibody cemiplimab has demonstrated effectiveness in the setting of locally advanced basal cell carcinoma (BCC) and squamous cell carcinoma. We describe a case of a large, locally invasive basosquamous carcinoma, an aggressive type of BCC, invading the left sternocleidomastoid muscle with near compression of the left internal jugular vein producing a severe anaemia secondary to ulceration and chronic blood loss. The patient was initially started on vismodegib monotherapy but failed to respond. He was then started on cemiplimab in addition to vismodegib. Improvement was noted after one cycle. After 21 cycles of cemiplimab, the left shoulder ulcerated lesion was completely re-epithelialised. He remains in complete remission after 31 cycles of cemiplimab in addition to vismodegib.


Assuntos
Antineoplásicos , Carcinoma Basocelular , Carcinoma Basoescamoso , Neoplasias Cutâneas , Masculino , Humanos , Carcinoma Basoescamoso/tratamento farmacológico , Neoplasias Cutâneas/patologia , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico
18.
Am J Case Rep ; 24: e938537, 2023 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-37978795

RESUMO

BACKGROUND Early therapies for metastatic melanoma improved patient quality of life; however, median survival remained unaffected. Studies are showing that surgical excision with the combination of immune checkpoint inhibitor (ICI) therapy has better outcomes than systemic therapy alone. This single-center case series describes 7 patients with oligometastatic melanoma treated by metastasectomy in combination with ICI and BRAF inhibitors. CASE REPORT One female and 6 male patients are included in our study, with ages ranging from 34 to 82 years. Oligometastatic melanoma is defined was having no more than 5 metastatic regions. Each patient had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received either ICI therapy with ipilimumab, nivolumab, and/or pembrolizumab, or targeted therapy with encorafenib and binimetinib, or a combination. Patients underwent metastasectomies with curative intent. The main outcome and measurements obtained were the duration of disease-free survival, based on radiographic evidence. The range of disease-free survival in our population was 13 to 67 months, with the lower end limited by patient death and the upper limit being the present day. CONCLUSIONS This case series reiterates survival benefit for patients who received metastasectomy after exhibiting good response to ICI therapy. ICI and/or BRAF inhibitor therapy combined with metastasectomy provides a possible curative option for patients who may have previously been relegated to palliative-focused care. By using a multimodal approach with oncologists and surgeons, we can challenge our understanding of what constitutes a resectable cancer.


Assuntos
Melanoma , Metastasectomia , Humanos , Masculino , Feminino , Proteínas Proto-Oncogênicas B-raf/uso terapêutico , Qualidade de Vida , Melanoma/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
19.
J Immunother Cancer ; 11(10)2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37852736

RESUMO

Since the first approval for immune checkpoint inhibitors (ICIs) for the treatment of cutaneous melanoma more than a decade ago, immunotherapy has completely transformed the treatment landscape of this chemotherapy-resistant disease. Combination regimens including ICIs directed against programmed cell death protein 1 (PD-1) with anti-cytotoxic T lymphocyte antigen-4 (CTLA-4) agents or, more recently, anti-lymphocyte-activation gene 3 (LAG-3) agents, have gained regulatory approvals for the treatment of metastatic cutaneous melanoma, with long-term follow-up data suggesting the possibility of cure for some patients with advanced disease. In the resectable setting, adjuvant ICIs prolong recurrence-free survival, and neoadjuvant strategies are an active area of investigation. Other immunotherapy strategies, such as oncolytic virotherapy for injectable cutaneous melanoma and bispecific T-cell engager therapy for HLA-A*02:01 genotype-positive uveal melanoma, are also available to patients. Despite the remarkable efficacy of these regimens for many patients with cutaneous melanoma, traditional immunotherapy biomarkers (ie, programmed death-ligand 1 expression, tumor mutational burden, T-cell infiltrate and/or microsatellite stability) have failed to reliably predict response. Furthermore, ICIs are associated with unique toxicity profiles, particularly for the highly active combination of anti-PD-1 plus anti-CTLA-4 agents. The Society for Immunotherapy of Cancer (SITC) convened a panel of experts to develop this clinical practice guideline on immunotherapy for the treatment of melanoma, including rare subtypes of the disease (eg, uveal, mucosal), with the goal of improving patient care by providing guidance to the oncology community. Drawing from published data and clinical experience, the Expert Panel developed evidence- and consensus-based recommendations for healthcare professionals using immunotherapy to treat melanoma, with topics including therapy selection in the advanced and perioperative settings, intratumoral immunotherapy, when to use immunotherapy for patients with BRAFV600-mutated disease, management of patients with brain metastases, evaluation of treatment response, special patient populations, patient education, quality of life, and survivorship, among others.


Assuntos
Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/tratamento farmacológico , Qualidade de Vida , Imunoterapia , Melanoma Maligno Cutâneo
20.
J Immunother Cancer ; 10(5)2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35545318

RESUMO

BACKGROUND: Basal cell carcinoma (BCC) is the most common malignancy worldwide, yet the management of patients with advanced or metastatic disease is challenging, with limited treatment options. Recently, programmed death receptor 1 (PD-1) inhibition has demonstrated activity in BCC after prior Hedgehog inhibitor treatment. METHODS: We conducted a multicenter, retrospective analysis of BCC patients treated with PD-1 inhibitor therapy. We examined the efficacy and safety of PD-1 therapy, as well as clinical and pathological variables in association with outcomes. Progression-free survival (PFS), overall survival (OS) and duration of response (DOR) were calculated using Kaplan-Meier methodology. Toxicity was graded per Common Terminology Criteria for Adverse Events V.5.0. RESULTS: A total of 29 patients with BCC who were treated with PD-1 inhibition were included for analysis, including 20 (69.0%) with locally advanced and 9 (31.0%) with metastatic disease. The objective response rate was 31.0%, with five partial responses (17.2%), and four complete responses (13.8%). Nine patients had stable disease (31.0%), with a disease control rate of 62.1%. The median DOR was not reached. Median PFS was 12.2 months (95% CI 0.0 to 27.4). Median OS was 32.4 months (95% CI 18.1 to 46.7). Two patients (6.9%) developed grade 3 or higher toxicity, while four patients (13.8%) discontinued PD-1 inhibition because of toxicity. Higher platelets (p=0.022) and any grade toxicity (p=0.024) were significantly associated with disease control rate. CONCLUSIONS: The clinical efficacy of PD-1 inhibition among patients with advanced or metastatic BCC in this real-world cohort were comparable to published trial data. Further investigation of PD-1 inhibition is needed to define its optimal role for patients with this disease.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Carcinoma Basocelular/tratamento farmacológico , Carcinoma Basocelular/patologia , Proteínas Hedgehog , Humanos , Receptor de Morte Celular Programada 1/uso terapêutico , Estudos Retrospectivos , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia
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