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Risco infecioso associado à imunoterapia para o cancro : o caso das micobacterioses
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Resumo(s)
Nos últimos anos, a imunoterapia tem vindo a representar um enorme avanço na abordagem e tratamento de inúmeras neoplasias. Diversas classes de agentes foram desenvolvidas com o objetivo de potenciar a resposta imune à proliferação e infiltração de células tumorais, bloqueando a sua capacidade de evasão ao sistema imunitário. A diversidade de mecanismos terapêuticos encontra-se em expansão, contemplando inibidores do checkpoint imunológico, vacinas e transferência celular adotiva. Apesar dos resultados promissores e da aplicabilidade em várias neoplasias – melanoma, cancro do pulmão de não-pequenas células, carcinoma de células renais, linfoma de Hodgkin, entre outros – os inibidores de checkpoints imunológicos têm vindo a associar-se a eventos adversos imunomediados (irAE – imune-related adverse events) que emergem da sobrerregulação da resposta imunológica. Podemos estar perante efeitos tóxicos de qualquer órgão ou sistema (gastrointestinal, pulmonar, neurológico, renal, musculoesquelético, endocrinológico, cutâneo, hematológico, etc.) e classificamse consoante a sua gravidade: grau 1 e 2 caso sejam assintomáticos ou os sintomas sejam ligeiros, grau 3 quando limitam as atividades básicas de vida diária e grau 4 quando se tratam de situações potencialmente ameaçadoras de vida. Assim, o seu tratamento pode exigir o recurso a fármacos imunossupressores como glucocorticóides, outros agentes convencionais ou anticorpos monoclonais dirigidos contra interleucinas específicas, aumentando o risco infecioso nestes doentes. Deste modo, torna-se relevante abordar o impacto direto e indireto deste tipo de terapêuticas no desenvolvimento de complicações infeciosas e especificamente o risco acrescido de manifestações primárias ou reativação de algumas infeções, das quais a tuberculose e outras micobacterioses são um exemplo particularmente relevante. Objetivo: Elaborar uma revisão bibliográfica atualizada sobre o risco infecioso associado às novas terapêuticas imunológicas para o cancro, com particular enfoque na tuberculose e outras micobacterioses.
In recent years, immunotherapy has represented an enormous advance in the approach and treatment of numerous tumors. Several classes of agents have been developed with the aim of potentiating the immune response to the proliferation and infiltration of tumour cells, blocking their ability to evade the immune system. The diversity of therapeutic mechanisms is expanding, contemplating immune checkpoint inhibitors, vaccines and adoptive cell transfer. Despite promising results and applicability in various tumours - melanoma, nonsmall cell lung cancer, renal cell carcinoma, Hodgkin's lymphoma, among others – immune checkpoint inhibitors have been associated with immune-related adverse events (irAE) that emerge from overregulation of the immune response. There can be toxicities in any organ or system (gastrointestinal, pulmonary, neurological, renal, musculoskeletal, endocrinological, cutaneous, hematological, etc.) and they are classified according to their severity: grades 1 and 2 if they are asymptomatic or the symptoms are mild, grade 3 when they limit the basic activities of daily living and grade 4 when they are potentially life-threatening situations. Thus, their treatment may require the use of immunosuppressive drugs such as corticosteroids, other conventional agents or monoclonal antibodies directed against specific interleukins, increasing the risk of infection in these patients. Therefore, it is relevant to address the direct and indirect impact of this type of therapy on the development of infectious complications and specifically the increased risk of primary manifestations or reactivation of some infections, from which tuberculosis and other mycobacteriosis are a particularly good example. Objective: To prepare an updated literature review on the infectious risk associated with new immunological therapies for cancer, focusing on tuberculosis and other mycobacteria.
In recent years, immunotherapy has represented an enormous advance in the approach and treatment of numerous tumors. Several classes of agents have been developed with the aim of potentiating the immune response to the proliferation and infiltration of tumour cells, blocking their ability to evade the immune system. The diversity of therapeutic mechanisms is expanding, contemplating immune checkpoint inhibitors, vaccines and adoptive cell transfer. Despite promising results and applicability in various tumours - melanoma, nonsmall cell lung cancer, renal cell carcinoma, Hodgkin's lymphoma, among others – immune checkpoint inhibitors have been associated with immune-related adverse events (irAE) that emerge from overregulation of the immune response. There can be toxicities in any organ or system (gastrointestinal, pulmonary, neurological, renal, musculoskeletal, endocrinological, cutaneous, hematological, etc.) and they are classified according to their severity: grades 1 and 2 if they are asymptomatic or the symptoms are mild, grade 3 when they limit the basic activities of daily living and grade 4 when they are potentially life-threatening situations. Thus, their treatment may require the use of immunosuppressive drugs such as corticosteroids, other conventional agents or monoclonal antibodies directed against specific interleukins, increasing the risk of infection in these patients. Therefore, it is relevant to address the direct and indirect impact of this type of therapy on the development of infectious complications and specifically the increased risk of primary manifestations or reactivation of some infections, from which tuberculosis and other mycobacteriosis are a particularly good example. Objective: To prepare an updated literature review on the infectious risk associated with new immunological therapies for cancer, focusing on tuberculosis and other mycobacteria.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2023
Palavras-chave
Imunoterapia Inibidores de checkpoints Eventos adversos imunomediados Tuberculose Micobacteriose Imunossupressão