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Cancer Resistance to Immunotherapy

Rita Khoury,Annoir Shayya,Cendrella Bou Orm,Osama Zein Deen,Hady Ghanem

Published 2025 in Immuno

ABSTRACT

Immunotherapy has revolutionized cancer treatment. Despite its success across various malignancies, a significant proportion of patients either fail to respond (primary resistance) or relapse after an initial response (acquired resistance). This review explores the different mechanisms underlying resistance to immunotherapy, including tumor-intrinsic factors such as loss of antigen presentation, genetic, and epigenetic mutations. It also examines tumor-extrinsic contributors, such as immunosuppressive cells in the tumor microenvironment, checkpoint molecule upregulation, and microbiome influences. A comprehensive understanding of resistance mechanisms is essential for improving patient selection, developing combination therapies, and ultimately enhancing the efficacy and durability of immunotherapeutic interventions.

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