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Review
. 2022 May 30:9:875974.
doi: 10.3389/fmed.2022.875974. eCollection 2022.

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

Patricia Iranzo  1 , Ana Callejo  1 , Juan David Assaf  1 , Gaspar Molina  1 , Daniel Esteban Lopez  1 , David Garcia-Illescas  1 , Nuria Pardo  1 , Alejandro Navarro  1 , Alex Martinez-Marti  1 , Susana Cedres  1 , Caterina Carbonell  2 , Joan Frigola  2 , Ramon Amat  2 , Enriqueta Felip  1
Affiliations
Review

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

Patricia Iranzo et al. Front Med (Lausanne). .

Abstract

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.

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

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Conflict of interest statement

AC reports advisory role and/or travel compensation: Bristol-Myers Squibb Recipient, F. Hoffmann La Roche AG, Pfizer, Boehringer Ingelheim, MSD Oncology, Leo Pharma, Medscape, and Kern Pharma. PI reports advisory role and/or travel compensation: Bristol-Myers Squibb Recipient, F. Hoffmann, La Roche AG, Merck Sharp & Dohme, Boehringer Ingelheim, MSD Oncology, Rovi, Kyowa Kirin, Grunenthal Pharma S.A., Pfizer, Medscape, Kern Pharma. NP reports advisory role and/or travel compensation: MSD oncology, Merck Sharp & Dohme, Bristol-Myers Squibb Recipient, F. Hoffmann La Roche AG, Pfizer, Boehringer Ingelheim, Grunenthal Pharma S.A Kern Pharma. AN reports advisory role, speaker's bureau or travel compensation: Bristol-Myers Squibb, F. Hoffmann La Roche AG, Pfizer, Boehringer Ingelheim, Oryzon Ge-nomics, Pfizer, AstraZeneca. AM-M provided consultation, attended advisory boards and/or speaker's bureau for the following organizations: Bristol-Myers Squibb, Lilly, F. Roche, MSD oncology, Pfizer, Boehringer Ingelheim, AstraZeneca. SC Bristol-Myers Squibb Recipient F, Hoffmann La Roche AG, Pfizer, Boehringer Ingelheim, MSD Oncology, Amphera. CC and JF had been partially supported by Grant for Oncology EMD Serono research funding to EF. EF reports consulting, advisory role or speaker's bureau: AbbVie, AstraZeneca, Blueprint medicines, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Eli Lilly, Guardant Health, Janssen, Medscape, Merck KGaA, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Takeda, Touchtime and research funding with: Fundación Merck Salud, Grant for Oncology Innovation EMD Serono. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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