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[PMID]:29381830
[Au] Autor:Sioud M
[Ad] Endereço:Department of Cancer Immunology, Oslo University Hospital, The Norwegian Radium Hospital, Montebello, Oslo, Norway.
[Ti] Título:T-cell cross-reactivity may explain the large variation in how cancer patients respond to checkpoint inhibitors.
[So] Source:Scand J Immunol;87(3), 2018 Mar.
[Is] ISSN:1365-3083
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The therapeutic use of the immune system to specifically attack tumours has been a long-standing vision among tumour immunologists. Recently, the use of checkpoint inhibitors to turn-off immunosuppressive signals has proven to be effective in enhancing T-cell reactivity against patient-specific neoantigens, resulting from somatic mutations. Several of the identified T-cell epitopes share similarity with common bacterial and viral antigens, suggesting the involvement of pre-existing microbial cross-reactive T cells in rapid and durable tumour regression seen in some patients. This notion of T-cell cross-reactivity is further supported by the findings that intestinal bacteria can influence checkpoint-blockade therapy. Moreover, early data indicate the presence of such T cells in long-term survival breast cancer patients. This review highlights the main challenges for cancer immunotherapy and discusses the potential contribution of T-cell cross-reactivity in cancer immunotherapy and whether it can be used as a biomarker to predict the responsiveness to checkpoint inhibitors.
[Mh] Termos MeSH primário: Reações Cruzadas/imunologia
Imunoterapia/métodos
Neoplasias/imunologia
Neoplasias/terapia
Linfócitos T/imunologia
[Mh] Termos MeSH secundário: Antígenos de Bactérias/imunologia
Antígenos de Neoplasias/imunologia
Antígenos Virais/imunologia
Biomarcadores Tumorais/imunologia
Antígeno CTLA-4/antagonistas & inibidores
Células Dendríticas/imunologia
Epitopos de Linfócito T/imunologia
Seres Humanos
Ativação Linfocitária/imunologia
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Receptores Imunológicos/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antigens, Bacterial); 0 (Antigens, Neoplasm); 0 (Antigens, Viral); 0 (Biomarkers, Tumor); 0 (CTLA-4 Antigen); 0 (Epitopes, T-Lymphocyte); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 0 (Receptors, Immunologic); 0 (TIGIT protein, human)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180131
[St] Status:MEDLINE
[do] DOI:10.1111/sji.12643


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[PMID]:29322203
[Au] Autor:Dada R
[Ad] Endereço:Department of Oncology MBC J-64, King Faisal Specialist Hospital and Research Center, P.O. Box 40047, Jeddah, 21499, Kingdom of Saudi Arabia. rdada@kfshrc.edu.sa.
[Ti] Título:Program death inhibitors in classical Hodgkin's lymphoma: a comprehensive review.
[So] Source:Ann Hematol;97(4):555-561, 2018 Apr.
[Is] ISSN:1432-0584
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:Cancer cells are able to induce immune system tolerance through different mechanisms. Recent achievements in the understanding of tumor microenvironment, invasion, and metastasizing have contributed to accelerated drug developments and approvals. Hodgkin lymphoma (HL) cells are the minority in a lymphocyte-rich microenvironment of HL tissue. The program death-1 (PD-1)/PD-ligand-1 checkpoint is one of the known effective pathways in classical HL to escape the immune system cells. The approval of PD-1 inhibitors in different cancer types with exciting response rates is truly revolutionizing our treatment armamentarium against cancer in general and classical HL in specific. Although the disease is one of the most curable tumors, we still need better outcome with more gentle treatment, especially for relapsed and refractory (r/r) patients. In this article, we review the current literature on immune checkpoint inhibitors and currently ongoing studies with nivolumab and pembrolizumab in r/r classical HL.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
Antígeno B7-H1/antagonistas & inibidores
Doença de Hodgkin/tratamento farmacológico
Proteínas de Neoplasias/antagonistas & inibidores
Receptor de Morte Celular Programada 1/antagonistas & inibidores
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/efeitos adversos
Anticorpos Monoclonais/uso terapêutico
Anticorpos Monoclonais Humanizados/efeitos adversos
Anticorpos Monoclonais Humanizados/uso terapêutico
Antineoplásicos/efeitos adversos
Antineoplásicos Imunológicos/efeitos adversos
Antineoplásicos Imunológicos/uso terapêutico
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
Antígeno B7-H1/metabolismo
Aprovação de Drogas
Resistência a Múltiplos Medicamentos
Resistência a Medicamentos Antineoplásicos
Doença de Hodgkin/metabolismo
Seres Humanos
Terapia de Alvo Molecular/efeitos adversos
Proteínas de Neoplasias/metabolismo
Receptor de Morte Celular Programada 1/metabolismo
Qualidade de Vida
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antibodies, Monoclonal, Humanized); 0 (Antineoplastic Agents); 0 (Antineoplastic Agents, Immunological); 0 (B7-H1 Antigen); 0 (CD274 protein, human); 0 (Neoplasm Proteins); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 31YO63LBSN (nivolumab); DPT0O3T46P (pembrolizumab)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180112
[St] Status:MEDLINE
[do] DOI:10.1007/s00277-017-3226-0


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[PMID]:28922790
[Au] Autor:Marisa L; Svrcek M; Collura A; Becht E; Cervera P; Wanherdrick K; Buhard O; Goloudina A; Jonchère V; Selves J; Milano G; Guenot D; Cohen R; Colas C; Laurent-Puig P; Olschwang S; Lefèvre JH; Parc Y; Boige V; Lepage C; André T; Fléjou JF; Dérangère V; Ghiringhelli F; de Reynies A; Duval A
[Ad] Endereço:Programme "Cartes d'Identité des Tumeurs," Ligue Nationale Contre le Cancer, Paris, France; INSERM, UMRS 938 - Centre de Recherche Saint-Antoine, Equipe "Instabilité des Microsatellites et Cancers," Equipe labellisée par la Ligue Nationale contre le Cancer, Paris, France; Sorbonne Université, UPMC U
[Ti] Título:The Balance Between Cytotoxic T-cell Lymphocytes and Immune Checkpoint Expression in the Prognosis of Colon Tumors.
[So] Source:J Natl Cancer Inst;110(1), 2018 Jan 01.
[Is] ISSN:1460-2105
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI). Their associations with patient survival were analyzed by Cox models, taking into account the microsatellite instability (MSI) status and affiliation with various Consensus Molecular Subgroups (CMS). PD-L1 and CD8 expression were examined on a subset of tumors with immunohistochemistry. All statistical tests were two-sided. Results: The expression of Immunoscore-like metagenes was statistically significantly associated with improved outcome in non-MSI tumors displaying low levels of both CTLs and immune checkpoints (ICKs; CMS2 and CMS3; hazard ratio [HR] = 0.63, 95% confidence interval [CI] = 0.43 to 0.92, P = .02; and HR = 0.55, 95% CI = 0.34 to 0.90, P = .02, respectively), but clearly had no prognostic relevance in CRCs displaying higher levels of CTLs and ICKs (CMS1 and CMS4; HR = 0.46, 95% CI = 0.10 to 2.10, P = .32; and HR = 1.13, 95% CI = 0.79 to 1.63, P = .50, respectively), including MSI tumors. ICK metagene expression was statistically significantly associated with worse prognosis independent of tumor staging in MSI tumors (HR = 3.46, 95% CI = 1.41 to 8.49, P = .007). ICK expression had a negative impact on the proliferation of infiltrating CD8 T cells in MSI neoplasms (median = 0.56 in ICK low vs median = 0.34 in ICK high, P = .004). Conclusions: ICK expression cancels the prognostic relevance of CTLs in highly immunogenic colon tumors and predicts a poor outcome in MSI CRC patients.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/genética
Biomarcadores Tumorais/imunologia
Neoplasias Colorretais/genética
Neoplasias Colorretais/imunologia
Linfócitos do Interstício Tumoral
Linfócitos T Citotóxicos
[Mh] Termos MeSH secundário: Antígenos CD/genética
Antígeno B7-H1/análise
Antígeno B7-H1/genética
Antígenos CD8/análise
Antígeno CTLA-4/genética
Colo/química
Neoplasias Colorretais/química
Neoplasias Colorretais/patologia
Feminino
Expressão Gênica
Receptor Celular 2 do Vírus da Hepatite A/genética
Seres Humanos
Proteína Coestimuladora de Linfócitos T Induzíveis/genética
Masculino
Instabilidade de Microssatélites
Meia-Idade
Estadiamento de Neoplasias
Prognóstico
Proteína 2 Ligante de Morte Celular Programada 1/genética
Receptor de Morte Celular Programada 1/genética
Estudos Retrospectivos
Taxa de Sobrevida
Células Th1
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antigens, CD); 0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD223 antigen); 0 (CD274 protein, human); 0 (CD8 Antigens); 0 (CTLA-4 Antigen); 0 (HAVCR2 protein, human); 0 (Hepatitis A Virus Cellular Receptor 2); 0 (ICOS protein, human); 0 (Inducible T-Cell Co-Stimulator Protein); 0 (PDCD1 protein, human); 0 (PDCD1LG2 protein, human); 0 (Programmed Cell Death 1 Ligand 2 Protein); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170920
[St] Status:MEDLINE
[do] DOI:10.1093/jnci/djx136


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[PMID]:28453847
[Au] Autor:Khoury G; Fromentin R; Solomon A; Hartogensis W; Killian M; Hoh R; Somsouk M; Hunt PW; Girling V; Sinclair E; Bacchetti P; Anderson JL; Hecht FM; Deeks SG; Cameron PU; Chomont N; Lewin SR
[Ad] Endereço:The Peter Doherty Institute for Infection and Immunity, University of Melbourne and Royal Melbourne Hospital, Australia.
[Ti] Título:Human Immunodeficiency Virus Persistence and T-Cell Activation in Blood, Rectal, and Lymph Node Tissue in Human Immunodeficiency Virus-Infected Individuals Receiving Suppressive Antiretroviral Therapy.
[So] Source:J Infect Dis;215(6):911-919, 2017 03 15.
[Is] ISSN:1537-6613
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Background: Immune activation and inflammation remain elevated in human immunodeficiency virus (HIV)-infected individuals receiving antiretroviral therapy (ART) and may contribute to HIV persistence. Methods: Using flow cytometry expression of CD38, HLA-DR and PD-1 were measured in blood (n = 48), lymph node (LN; n = 9), and rectal tissue (n = 17) from virally suppressed individuals. Total and integrated HIV DNA, 2-LTR circles, and cell-associated unspliced HIV RNA were quantified. Results: CD4+ T cells from rectal tissue had a higher frequency of integrated HIV DNA compared with blood (4.26 fold-change in DNA; 95% confidence interval [CI] = 2.61-7.00; P < .001) and LN (2.32 fold-change in DNA; 95% CI = 1.22-4.41; P = .01). In rectal tissue, there were positive associations between integrated HIV DNA with PD-1+ CD4+ T-cells (1.44 fold-change in integrated HIV DNA per 10-unit increase in PD-1+ CD4+ T cells; 95% CI = 1.01-2.05; P = .045) and CD38+HLA-DR+ CD8+ T cells (1.40 fold-change in integrated HIV DNA per 1-unit increase in CD38+HLA-DR+ CD8+ T cells; 95% CI = 1.05-1.86; P = .02). Both associations were independent of current and nadir CD4+ T-cell counts. Conclusions: During ART, rectal tissue is an important reservoir for HIV persistence with a high frequency of activated CD4+ and CD8+ T cells. PD-1 may represent a marker of HIV persistence in rectal tissue.
[Mh] Termos MeSH primário: Linfócitos T CD4-Positivos/imunologia
Linfócitos T CD8-Positivos/imunologia
Infecções por HIV/tratamento farmacológico
Infecções por HIV/imunologia
Ativação Linfocitária
[Mh] Termos MeSH secundário: Terapia Antirretroviral de Alta Atividade
Austrália
Biomarcadores/metabolismo
Contagem de Linfócito CD4
Estudos Transversais
DNA Viral/sangue
Feminino
HIV-1/imunologia
Antígenos HLA-DR/análise
Seres Humanos
Linfonodos/imunologia
Masculino
Meia-Idade
Receptor de Morte Celular Programada 1/metabolismo
Reto/imunologia
Análise de Regressão
Fatores Sexuais
Estados Unidos
Carga Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Biomarkers); 0 (DNA, Viral); 0 (HLA-DR Antigens); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE
[do] DOI:10.1093/infdis/jix039


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[PMID]:28460468
[Au] Autor:Jiang L; Su X; Zhang T; Yin X; Zhang M; Fu H; Han H; Sun Y; Dong L; Qian J; Xu Y; Fu X; Gavine PR; Zhou Y; Tian K; Huang J; Shen D; Jiang H; Yao Y; Han B; Gu Y
[Ad] Endereço:Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
[Ti] Título:PD-L1 expression and its relationship with oncogenic drivers in non-small cell lung cancer (NSCLC).
[So] Source:Oncotarget;8(16):26845-26857, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In order to explore the potential patient population who could benefit from anti PD-1/PD-L1 mono or combination therapies, this study aimed to profile a panel of immunotherapy related biomarkers (PD-1, PD-L1, CTLA-4 and CD8) and targeted therapy biomarkers (EGFR, KRAS, ALK, ROS1 and MET) in NSCLC.Tumor samples from 297 NSCLC patients, including 156 adenocarcinomas (AD) and 129 squamous cell carcinomas (SCC), were analyzed using immunohistochemistry, immunofluorescence, sequencing and fluorescence in situ hybridization.43.1% of NSCLC patients had PD-L1 positive staining on ≥ 5% tumor cells (TC). Furthermore, dual color immunofluorescence revealed that the majority of PD-L1/CD8 dual positive tumor infiltrating lymphocytes (TIL) had infiltrated into the tumor core. Finally, combined analysis of all eight biomarkers showed that tumor PD-L1 positivity overlapped with known alterations in NSCLC oncogenic tumor drivers in 26% of SCC and 76% of AD samples.Our illustration of the eight biomarkers' overlap provides an intuitive overview of NSCLC for personalized therapeutic strategies using anti-PD-1/PD-L1 immune therapies, either as single agents, or in combination with targeted therapies. For the first time, we also report that PD-L1 and CD8 dual positive TILs are predominantly located within the tumor core.
[Mh] Termos MeSH primário: Antígeno B7-H1/genética
Biomarcadores Tumorais
Carcinoma Pulmonar de Células não Pequenas/genética
Carcinoma Pulmonar de Células não Pequenas/patologia
Expressão Gênica
Neoplasias Pulmonares/genética
Neoplasias Pulmonares/patologia
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Antígeno B7-H1/metabolismo
Antígeno CTLA-4/genética
Antígeno CTLA-4/metabolismo
Carcinoma Pulmonar de Células não Pequenas/metabolismo
Carcinoma Pulmonar de Células não Pequenas/cirurgia
Transformação Celular Neoplásica/genética
Feminino
Amplificação de Genes
Seres Humanos
Imuno-Histoquímica
Hibridização in Situ Fluorescente
Neoplasias Pulmonares/metabolismo
Neoplasias Pulmonares/cirurgia
Linfócitos do Interstício Tumoral/imunologia
Linfócitos do Interstício Tumoral/metabolismo
Masculino
Meia-Idade
Mutação
Gradação de Tumores
Estadiamento de Neoplasias
Receptor de Morte Celular Programada 1/genética
Receptor de Morte Celular Programada 1/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD274 protein, human); 0 (CTLA-4 Antigen); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15839


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[PMID]:28460462
[Au] Autor:Ness N; Andersen S; Khanehkenari MR; Nordbakken CV; Valkov A; Paulsen EE; Nordby Y; Bremnes RM; Donnem T; Busund LT; Richardsen E
[Ad] Endereço:Department of Medical Biology, UiT The Arctic University of Norway, N-9037 Tromso, Norway.
[Ti] Título:The prognostic role of immune checkpoint markers programmed cell death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) in a large, multicenter prostate cancer cohort.
[So] Source:Oncotarget;8(16):26789-26801, 2017 Apr 18.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Programmed cell death protein 1 (PD-1) and its ligand Programmed death ligand 1 (PD-L1) have gained massive attention in cancer research due to recent availability and their targeted antitumor effects. Their role in prostate cancer is still undetermined. We constructed tissue microarrays from prostatectomy specimens from 535 prostate cancer patients. Following validation of antibodies, immunohistochemistry was used to evaluate the expression of PD-1 in lymphocytes and PD-L1 in epithelial and stromal cells of primary tumors. PD-L1 expression was commonly seen in tumor epithelial cells (92% of cases). Univariate survival analysis revealed a positive association between a high density of PD-1+ lymphocytes and worse clinical failure-free survival, limited to a trend (p = 0.084). In subgroups known to indicate unfavorable prostate cancer prognosis (Gleason grade 9, age < 65, preoperative PSA > 10, pT3) patients with high density of PD-1+ lymphocytes had a significantly higher risk of clinical failure (p = < 0.001, p = 0.025, p = 0.039 and p = 0.011, respectively). In the multivariate analysis, high density of PD-1+ lymphocytes was a significant negative independent prognostic factor for clinical failure-free survival (HR = 2.48, CI 95% 1.12-5.48, p = 0.025).
[Mh] Termos MeSH primário: Antígeno B7-H1/metabolismo
Biomarcadores Tumorais
Imunomodulação
Receptor de Morte Celular Programada 1/metabolismo
Neoplasias da Próstata/imunologia
Neoplasias da Próstata/metabolismo
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Fibroblastos Associados a Câncer/metabolismo
Seres Humanos
Imuno-Histoquímica
Imunofenotipagem
Linfócitos do Interstício Tumoral/imunologia
Linfócitos do Interstício Tumoral/metabolismo
Masculino
Meia-Idade
Gradação de Tumores
Estadiamento de Neoplasias
Prognóstico
Neoplasias da Próstata/mortalidade
Neoplasias da Próstata/patologia
Reprodutibilidade dos Testes
Análise Serial de Tecidos
Carga Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD274 protein, human); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.15817


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[PMID]:28463153
[Au] Autor:Bang A; Wilhite TJ; Pike LRG; Cagney DN; Aizer AA; Taylor A; Spektor A; Krishnan M; Ott PA; Balboni TA; Hodi FS; Schoenfeld JD
[Ad] Endereço:Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, Massachusetts; Division of Radiation Oncology, University of Ottawa, Ottawa, Ontario, Canada.
[Ti] Título:Multicenter Evaluation of the Tolerability of Combined Treatment With PD-1 and CTLA-4 Immune Checkpoint Inhibitors and Palliative Radiation Therapy.
[So] Source:Int J Radiat Oncol Biol Phys;98(2):344-351, 2017 06 01.
[Is] ISSN:1879-355X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:PURPOSE: To analyze immune-related adverse events (ir-AEs) in patients treated with radiation and immune checkpoint blockade. METHODS AND MATERIALS: We retrospectively reviewed records from patients with metastatic non-small cell lung cancer, melanoma, or renal cell cancer who received at least 1 cycle of a CTLA-4 or PD-1 inhibitor and radiation. Immune-related adverse events, defined using Common Terminology Criteria for Adverse Events version 4.0, were tabulated in relation to treatment variables, and associations with sequencing and timing were assessed. RESULTS: We identified 133 patients, of whom 28 received a CTLA-4 inhibitor alone, 88 received a PD-1 inhibitor alone, and 17 received both classes of inhibitors either sequentially (n=13) or concurrently (n=4). Fifty-six patients received radiation within 14 days of an immune checkpoint inhibitor. Forty-six patients experienced at least 1 ir-AE (34.6%). Patients receiving both CTLA-4 and PD-1 inhibitors experienced more any-grade ir-AEs as compared with either individually (71% vs 29%, P=.0008). Any-grade ir-AEs occurred in 39% of patients in whom radiation was administered within 14 days of immunotherapy, compared with 23% of other patients (P=.06) and more often in patients who received higher equivalent dose in 2-Gy fractions (EQD2) EQD2 (P=.01). However, most toxicities were mild. There were no associations between site irradiated and specific ir-AEs. CONCLUSIONS: Our data suggest the combination of focal palliative radiation and CTLA-4 and/or PD-1 inhibitors is well tolerated, with manageable ir-AEs that did not seem to be associated with the particular site irradiated. Although conclusions are limited by the heterogeneity of patients and treatments, and future confirmatory studies are needed, this information can help guide clinical practice for patients receiving immune checkpoint therapy who require palliative radiation therapy.
[Mh] Termos MeSH primário: Antígeno CTLA-4/antagonistas & inibidores
Carcinoma Pulmonar de Células não Pequenas/terapia
Carcinoma de Células Renais/terapia
Pontos de Checagem do Ciclo Celular/imunologia
Imunoterapia/efeitos adversos
Neoplasias Renais/terapia
Neoplasias Pulmonares/terapia
Melanoma/terapia
Receptor de Morte Celular Programada 1/antagonistas & inibidores
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Carcinoma Pulmonar de Células não Pequenas/secundário
Carcinoma de Células Renais/secundário
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Colite/etiologia
Terapia Combinada/efeitos adversos
Terapia Combinada/métodos
Dermatite/etiologia
Feminino
Seres Humanos
Imunoterapia/métodos
Neoplasias Renais/patologia
Neoplasias Pulmonares/patologia
Masculino
Melanoma/secundário
Meia-Idade
Cuidados Paliativos/métodos
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (CTLA-4 Antigen); 0 (CTLA4 protein, human); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:27776977
[Au] Autor:Singh P; Black P
[Ad] Endereço:Division of Hematology and Oncology , Mayo clinic, Phoenix, AZ. Electronic address: drparminder.singh@me.com.
[Ti] Título:Emerging role of checkpoint inhibition in localized bladder cancer.
[So] Source:Urol Oncol;34(12):548-555, 2016 12.
[Is] ISSN:1873-2496
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Checkpoint inhibitors have rapidly become a standard treatment option for metastatic urothelial carcinoma. A wave of enthusiasm for these drugs has pushed them also into the setting of localized bladder cancer, including both non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive disease bladder cancer (MIBC). Here, we aimed to review the emerging role of checkpoint inhibition in localized bladder cancer. METHODS: We reviewed the current treatment landscape for both NMIBC and MIBC and established a significant unmet clinical need for novel therapies. We have compiled the evidence that supports the investigation of checkpoint blockade in localized bladder cancer and have reviewed the corresponding clinical trial׳s landscape. RESULTS: The success of checkpoint inhibitors in metastatic bladder cancer offers the most compelling rationale for testing checkpoint blockade in localized disease. The established benefit of intravesical Bacillus Calmette-Guérin provides precedent for immune therapy in bladder cancer. Immune dysfunction has been described in bladder cancer, and we know that checkpoint molecules are expressed in these tumors. Furthermore, the high neoantigen burden of bladder cancer and results from preclinical studies suggest that checkpoint blockade deserves testing in earlier stage disease. Multiple trials are either planned or underway in almost all bladder cancer disease states. CONCLUSION: Ongoing trials would determine in the next several years whether checkpoint inhibitors can have a similar effect in localized disease as they have had in metastatic bladder cancer. They would also determine if patients with earlier disease would tolerate the toxicity of systemic therapy. The future holds promise for predictive biomarkers to guide individualized use of these agents and for effective combination therapies to overcome resistances.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/uso terapêutico
Carcinoma de Células de Transição/terapia
Imunoterapia
Terapia de Alvo Molecular
Neoplasias da Bexiga Urinária/terapia
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/uso terapêutico
Antineoplásicos Imunológicos/efeitos adversos
Antígeno B7-H1/antagonistas & inibidores
Antígeno B7-H1/imunologia
Antígeno CTLA-4/antagonistas & inibidores
Antígeno CTLA-4/imunologia
Carcinoma de Células de Transição/tratamento farmacológico
Carcinoma de Células de Transição/imunologia
Carcinoma de Células de Transição/cirurgia
Ensaios Clínicos como Assunto
Terapia Combinada
Cistectomia
Seres Humanos
Ipilimumab/uso terapêutico
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Receptor de Morte Celular Programada 1/imunologia
Radioterapia Adjuvante
Subpopulações de Linfócitos T/efeitos dos fármacos
Subpopulações de Linfócitos T/imunologia
Evasão Tumoral
Neoplasias da Bexiga Urinária/tratamento farmacológico
Neoplasias da Bexiga Urinária/imunologia
Neoplasias da Bexiga Urinária/cirurgia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents, Immunological); 0 (B7-H1 Antigen); 0 (CD274 protein, human); 0 (CTLA-4 Antigen); 0 (Ipilimumab); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 52CMI0WC3Y (atezolizumab)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161026
[St] Status:MEDLINE


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[PMID]:27773553
[Au] Autor:Park JC; Hahn NM
[Ad] Endereço:Department of Oncology at the Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University in Baltimore, Baltimore, MD.
[Ti] Título:Emerging role of immunotherapy in urothelial carcinoma-Future directions and novel therapies.
[So] Source:Urol Oncol;34(12):566-576, 2016 12.
[Is] ISSN:1873-2496
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Tremendous advances in our understanding of the tumor immunology and molecular biology of urothelial carcinoma (UC) have led to the recent approval of immunotherapy as a novel option for patients with UC with advanced disease. Despite the promising data of novel immune checkpoint inhibitors, only a small subset of patients with UC achieves durable remissions. Because an optimal antitumor response requires coordination of multiple immune, tumor, and microenvironment effector cells, novel approaches targeting distinct mechanisms of action likely in combination are needed. In addition, discovery of reliable immune biomarkers, understanding of mechanisms of resistance, and novel clinical trial designs are warranted for maximum benefit of UC immunotherapy.
[Mh] Termos MeSH primário: Antineoplásicos Imunológicos/uso terapêutico
Carcinoma de Células de Transição/terapia
Imunoterapia
Terapia de Alvo Molecular
Terapias em Estudo
Neoplasias da Bexiga Urinária/terapia
[Mh] Termos MeSH secundário: Anticorpos Monoclonais/efeitos adversos
Anticorpos Monoclonais/uso terapêutico
Antineoplásicos Imunológicos/efeitos adversos
Antígeno B7-H1/antagonistas & inibidores
Antígeno B7-H1/imunologia
Biomarcadores Tumorais
Carcinoma de Células de Transição/tratamento farmacológico
Carcinoma de Células de Transição/imunologia
Ensaios Clínicos como Assunto
Receptores Coestimuladores e Inibidores de Linfócitos T/antagonistas & inibidores
Receptores Coestimuladores e Inibidores de Linfócitos T/imunologia
Previsões
Seres Humanos
Imunidade Inata
Imunoterapia Adotiva
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/imunologia
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Receptor de Morte Celular Programada 1/imunologia
Projetos de Pesquisa
Evasão Tumoral/efeitos dos fármacos
Evasão Tumoral/imunologia
Microambiente Tumoral/imunologia
Neoplasias da Bexiga Urinária/tratamento farmacológico
Neoplasias da Bexiga Urinária/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antineoplastic Agents, Immunological); 0 (B7-H1 Antigen); 0 (Biomarkers, Tumor); 0 (CD274 protein, human); 0 (Costimulatory and Inhibitory T-Cell Receptors); 0 (Neoplasm Proteins); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor); 31YO63LBSN (nivolumab); 52CMI0WC3Y (atezolizumab)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


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[PMID]:29228840
[Au] Autor:Chang A; Schlafer D; Flowers CR; Allen PB
[Ad] Endereço:a Department of Hematology and Medical Oncology , Winship Cancer Institute, Emory University School of Medicine , Atlanta , GA , USA.
[Ti] Título:Investigational PD-1 inhibitors in HL and NHL and biomarkers for predictors of response and outcome.
[So] Source:Expert Opin Investig Drugs;27(1):55-70, 2018 Jan.
[Is] ISSN:1744-7658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Inhibitors against the PD-1/PD-L1 pathway are revolutionizing the treatment and management of malignancies. Areas covered: We summarize our current understanding of the function of PD-1, its role in immune evasion, the clinical data available that support the use of PD-1 antagonist in Hodgkin and non-Hodgkin lymphomas, and potential predictors of response. Expert opinion: We anticipate that in the next 10 years, agents that modulate the immune system such as PD-1 antagonists will be increasingly used in favor over traditional cytotoxic chemotherapeutic agents. PD-1 antagonists will be combined with future immunotherapies or used as adjuncts to cellular therapy to boost tumor-specific immune responses.
[Mh] Termos MeSH primário: Antineoplásicos/uso terapêutico
Doença de Hodgkin/tratamento farmacológico
Linfoma não Hodgkin/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/farmacologia
Biomarcadores Tumorais/metabolismo
Desenho de Drogas
Drogas em Investigação/farmacologia
Drogas em Investigação/uso terapêutico
Doença de Hodgkin/imunologia
Doença de Hodgkin/patologia
Seres Humanos
Linfoma não Hodgkin/imunologia
Linfoma não Hodgkin/patologia
Receptor de Morte Celular Programada 1/antagonistas & inibidores
Receptor de Morte Celular Programada 1/imunologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Biomarkers, Tumor); 0 (Drugs, Investigational); 0 (PDCD1 protein, human); 0 (Programmed Cell Death 1 Receptor)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171213
[St] Status:MEDLINE
[do] DOI:10.1080/13543784.2018.1416091



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