Overview of Checkpoint Inhibitors Mechanism of Action: Role of Immune-Related Adverse Events and Their Treatment on Progression of Underlying Cancer

Frontiers in Medicine

article

Patricia Iranzo¹  Ana Callejo¹  Juan David Assaf¹  Gaspar Molina¹  Daniel Esteban Lopez¹  David Garcia-Illescas¹  Nuria Pardo¹  Alejandro Navarro¹  Alex Martinez-Marti¹  Susana Cedres¹  Caterina Carbonell²  Joan Frigola²  Ramon Amat²  Enriqueta Felip¹ 

[1] Medical Oncology Department, Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology;Thoracic Cancers Translational Genomics Unit, Vall d'Hebron Institute of Oncology

关键词: immune checkpoint inhibitors (ICIs);    immune-related adverse events (irAEs);    corticosteroids;    efficacy;    multidisciplinary management;   

DOI  :  10.3389/fmed.2022.875974

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

In recent years, immunotherapy-based regimens have been included into the treatment's algorithm of several cancer types. Programmed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) interact with their ligands found on the surface of antigen presenting cells (APC) or tumor cells (PD-L1/2 and CD80/86). Through these interactions, stimulatory or inhibitory signals are established. Immune checkpoint inhibitors (ICIs), block these interactions, and when administered not only as monotherapy but also as part of combination regimens, have shown to improve survival results in multiple advanced cancers leading to an increasing number of patients treated with ICI and, as a consequence, a rise in the number of patients developing immune-related adverse events (irAEs). Presence of irAEs has been associated with greater benefit from treatment, especially when blocking PD-L1. Recent data suggests that treatment benefit persists after discontinuation of ICIs due to a treatment related adverse event, regardless of the grade. Patients experiencing grade 3-4 irAEs are at risk of toxicity recurrence after reintroducing immunotherapy and therefore, the decision to resume the treatment is challenging. In these cases, a multidisciplinary approach is always needed and several factors should be considered. Management of severe toxicities may require systemic corticosteroids which can impact on T-cell function. Due to their immunosuppressive properties, it is necessary to deeper determine how corticosteroids influence responses. In terms of overall survival (OS), the use of steroids as therapy for irAEs seems not to reduce OS and several studies have reported durable responses in patients experiencing autoimmune toxicities treated with corticosteroids.

【 授权许可】

CC BY