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Principles of Checkpoint Inhibition in Malignant Lymphoma

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Cancer Immunotherapy

Part of the book series: Cancer Immunotherapy

Abstract

Malignancies manipulate the physiologic immune system through various immune checkpoint pathways to antagonize T cell activation and provide themselves an immune escape advantage. Targeting these inhibitory signals has been shown to be an effective approach to enhance the tumor-eradicating effect of the human immune system. Immune checkpoint inhibitors (ICIs) have emerged as a promising immunotherapy platform in several cancers. In lymphoma, pioneered in Hodgkin lymphoma (HL), inhibitors targeting program cell death-1 and its ligands have demonstrated excellent activity and have been incorporated into HL treatment paradigms. Despite excellent results in HL and some other lymphoma subtypes, the efficacy profile of ICIs in other lymphoma histologies has been modest and the implication of this lack of benefit remains to be explored. Moreover, despite initial responses, the response is not sustained in the majority of patients. The underlying reasons for the success or failure of ICI-based treatment are complicated and determined by several factors. Understanding the mechanisms of treatment failure and identifying predictive biomarkers will enable us to optimize immunotherapy in relapsing or non-responding patients. Lastly, many novel ICIs against different immune inhibitory axes are actively investigated in various settings, and hopefully these agents will overcome the limitations observed with the current ICIs.

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Acknowledgment

Kitsada Wudhikarn receives an education support grant from the King Chulalongkorn Memorial hospital, Thai Red Cross Society, Bangkok, Thailand.

Compliance with Ethical Standards

Disclosure of potential conflicts of interest: Kitsada Wudhikarn does not have any funding sources or conflicts of interest. Stephen M. Ansell receives research funding (to his institution) from Bristol Myers Squibb, Seattle Genetics, Regeneron, Trillium, AI Therapeutics and Affimed.

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  1. Division of Hematology, Department of Medicine, Mayo Clinic, Rochester, MN, USA

    Kitsada Wudhikarn & Stephen M. Ansell

  2. Division of Hematology and Research Unit in Translational Hematology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand

    Kitsada Wudhikarn

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Wudhikarn, K., Ansell, S.M. (2022). Principles of Checkpoint Inhibition in Malignant Lymphoma. In: Cancer Immunotherapy. Springer, Cham. https://doi.org/10.1007/13905_2022_18

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  • DOI: https://doi.org/10.1007/13905_2022_18

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