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1.
Allergol. immunopatol ; 47(3): 303-308, mayo-jun. 2019. tab
Artigo em Inglês | IBECS | ID: ibc-186494

RESUMO

Immunotherapy delivered a new therapeutic option to the oncologist: Ipilimumab (anti-CTLA-4), Nivolumab and Pembrolizumab (anti-PD1), and Atezolizumab (anti-PD-L1) increase overall survival and show a better safety profile compared to chemotherapy in patients with metastatic melanoma, lung, renal cancer among others. But all that glitters is not gold and there is an increasing number of reports of adverse effects while using immune-checkpoint inhibitors. While chemotherapy could weaken the immune system, this novel immunotherapy could hyper-activate it, resulting in a unique and distinct spectrum of adverse events, called immune-related adverse events (IRAEs). IRAEs, ranging from mild to potentially life-threatening events, can involve many systems, and their management is radically different from that of cytotoxic drugs: immunosuppressive treatments, such as corticoids, infliximab or mycophenolate mofetil, usually result in complete reversibility, but failing to do so can lead to severe toxicity or even death. Patient selection is an indirect way to reduce adverse events minimizing the number of subjects exposed to this drugs: unfortunately PDL-1, the actual predictive biomarker, would not allow clinicians select or exclude patients for treatment with checkpoint inhibitors


No dipsonible


Assuntos
Humanos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Imunossupressores/uso terapêutico , Imunoterapia/métodos , Ipilimumab/uso terapêutico , Neoplasias/terapia , Nivolumabe/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Antígeno HLA-B7/imunologia , Antígeno CTLA-4/imunologia , Sistema Imunitário/efeitos dos fármacos , Ipilimumab/efeitos adversos , Neoplasias/imunologia , Neoplasias/mortalidade , Receptor de Morte Celular Programada 1/imunologia
2.
Actas dermo-sifiliogr. (Ed. impr.) ; 110(5): 353-359, jun. 2019. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-180923

RESUMO

La inmunoterapia en el cáncer emerge como un tratamiento novedoso y prometedor en una gran variedad de tumores, incluido el cáncer cutáneo no melanoma. Los anticuerpos inhibidores de proteínas de control inmunitario están dirigidos fundamentalmente a las moléculas de superficie CTLA-4 (antígeno citotóxico de los linfocitos T) y PD-1 (molécula de muerte programada 1). En el presente artículo se revisan las vías de CTLA-4 y PD-1/PD-L1 (PD-1/ligando de la PD-1) y las evidencias actuales de tratamiento con inhibidores de puntos de control inmunitario en los principales tipos de cáncer cutáneo no melanoma


Immunotherapy is emerging as a new and promising treatment for a great variety of tumors, including nonmelanoma skin cancer. Checkpoint inhibitors -antibodies that block proteins that regulate the immune system- mainly target the surface protein CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) and the PD-1/PD-L1 (programmed cell death protein 1/PD-ligand 1) axis. We review the CTLA-4 and PD-1/PD-L1 pathways and current evidence supporting checkpoint inhibitor therapy in the main types of nonmelanoma skin cancer


Assuntos
Humanos , Imunoterapia , Neoplasias Cutâneas/terapia , Antígeno CTLA-4/antagonistas & inibidores , Antígeno B7-H1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Cutâneas/imunologia , Ativação Linfocitária/fisiologia , Carcinoma de Célula de Merkel/imunologia , Carcinoma de Célula de Merkel/terapia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/terapia , Carcinoma Basocelular/imunologia
3.
Clin. transl. oncol. (Print) ; 20(8): 966-974, ago. 2018. ilus, tab
Artigo em Inglês | IBECS | ID: ibc-173680

RESUMO

Antibodies against immune checkpoint inhibitors such as anti-programmed cell death protein 1 (PD-1) and anti-programmed death ligand 1 (PD-L1) play a key role in the treatment of advanced lung cancer. To examine the clinical benefits of these agents, preclinical and clinical studies have been conducted to identify definitive biomarkers associated with cancer status. Analysis of the blood and feces of tumor patients has attracted attention in recent studies attempting to identify non-invasive biomarkers such as cytokines, soluble PD-L1, peripheral blood mononuclear cells, and gut microbiota. These factors are believed to interact with each other to produce synergistic effects and contribute to the formation of the tumor immune microenvironment through the seven steps of the cancer immunity cycle. The immunogram was first introduced as a novel indicator to define the immunity status of cancer patients. In this review, we discuss the progress in the identification of predictive biomarkers as well as future prospects for anti-PD-1/PD-L1 therapy


No disponible


Assuntos
Humanos , Neoplasias/imunologia , Células Neoplásicas Circulantes/imunologia , Leucócitos Mononucleares/imunologia , Microbiota/imunologia , Anticorpos Monoclonais/uso terapêutico , Neoplasias/patologia , Biópsia/métodos , Biomarcadores Tumorais/análise , Receptor de Morte Celular Programada 1/imunologia , Microambiente Tumoral/imunologia , Antígenos B7/imunologia
4.
Arch. esp. urol. (Ed. impr.) ; 71(4): 393-399, mayo 2018. graf
Artigo em Espanhol | IBECS | ID: ibc-178416

RESUMO

La supervivencia a largo plazo para pacientes con cáncer avanzado de vejiga es precaria, con una supervivencia a 5 años de apenas el 5% en los casos metastásicos. Normalmente, la unión de PD-L1 a PD-1 altera la actividad inmunitaria modulándola para inhibir enfermedades autoinmunes e inflamaciones crónicas. Sin embargo, algunos canceres utilizan esta vía para bloquear la respuesta inmune del paciente y continuar creciendo. La nueva inmunoterapia contra el cáncer vesical pretende bloquear la capacidad de las células tumorales para resistir a la respuesta inmune del paciente mediante la actuación sobre los puntos de control de las células inmunitarias. Dichos fármacos son capaces de bloquear el receptor PD-1 presente en la superficie de los linfocitos, o bien los ligandos PD-L1 y PD-L2 expresados por las células cancerosas, esto impediría la unión de ambos bloqueando la señal inmunomoduladora y permitiendo que las células T continúen activas contra el tumor. La diana terapéutica del Pembrolizumab y el Nivolumab, es PD-1, la proteína receptora de PD-L1 en células inmunitarias. El resto de moléculas aprobadas para distintos tipos de cáncer como Atezolizumab, Avelumab o Durvalumab actúan sobre la proteína PD-L1 que es expresada en concentraciones altas en algunas células cancerosas. Los inhibidores del punto de control ofrecen una alternativa efectiva para los pacientes para los que anteriormente había pocas opciones de respuestas duraderas, incluidos aquellos que no son elegibles para los regímenes basados en cisplatino o que están en riesgo de toxicidad significativa. Esta revisión describe los datos más recientes sobre los agentes que inhiben la PD-L1, que se encuentran en la superficie de las células tumorales, y la PD-1 que se encuentra en las células T y B activadas y los macrófagos. Se están llevando a cabo investigaciones para categorizar aún más las respuestas, definir poblaciones de pacientes ideales e investigar combinaciones de inhibidores de puntos de control para abordar múltiples vías en el funcionamiento del sistema inmunitario


Long-term survival for patients with advanced bladder cancer is precarious, with a 5-year survival of just 5% in metastatic cases. Normally, the binding of PD-L1 to PD-1 alters the immune activity by modulating it to inhibit autoimmune diseases or chronic inflammation. However, some cancers use this route to block the immune response of the patient and continue growing. The new immunotherapy against bladder cancer aims to block the ability of tumor cells to resist patient's immune response by acting on the checkpoints of immune cells. These drugs are able to block the PD-1 receptor present on the surface of the lymphocytes, or the PD-L1 and PD-L2 ligands expressed by the cancer cells; this would prevent the binding of both blocking the immunomodulatory signal and allowing the T cells continue active against the tumor. The therapeutic target of Pembrolizumab and Nivolumab is PD-1, the receptor protein of PD-L1 in immune cells. The rest of molecules approved for different types of cancer such as Atezolizumab, Avelumab or Durvalumab act on the PD-L1 protein that is expressed in high concentrations in some cancer cells. The checkpoint inhibitors offer an effective alternative for patients for whom previously there were few options for durable responses, including those who are ineligible for cisplatin-based regimens or who are at risk of significant toxicity. This review describes the most recent data on agents that inhibit PD-L1, found on the surface of tumor cells, and PD-1 found on activated T and B cells and macrophages. Research is ongoing to further categorize responses, define ideal patient populations, and investigate combinations of checkpoint inhibitors to address multiple pathways in the functioning immune system


Assuntos
Humanos , Antígeno B7-H1/antagonistas & inibidores , Imunoterapia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias da Bexiga Urinária/imunologia
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