Immune evasion in cell-based immunotherapy: unraveling challenges and novel strategies

• Published in: Journal of biomedical science Vol. 31; no. 1; p. 5
• Main Authors: Li, Yan-Ruide, Halladay, Tyler, Yang, Lili
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 12.01.2024; BioMed Central; BMC
• Subjects: Antigen presentation; Antigens; Apoptosis; Cancer; Cancer therapies; CAR-engineered T (CAR-T) cell therapy; Care and treatment; Cell death; Cell therapy; Cell-based immunotherapies (CBIs); Chimeric antigen receptor (CAR); Chimeric antigen receptors; Cytotoxicity; Development and progression; Down-regulation; Genetic engineering; Health aspects; Humans; Immune checkpoint; Immune checkpoint proteins; Immune Evasion; Immune system; Immunosuppression; Immunotherapy; Immunotherapy, Adoptive; Ligands; Lymphocytes; Metastasis; Mutation; Neoplasms - therapy; Peptides; Prospective Studies; Proteins; Receptors, Chimeric Antigen - metabolism; Tumor cells; Tumor Microenvironment; Tumor microenvironment (TME); Tumors; Tumor microenvironment (TME); Tumor heterogeneity; Chimeric antigen receptor (CAR); Immune evasion; CAR-engineered T (CAR-T) cell therapy; Cell-based immunotherapies (CBIs); Immune checkpoint proteins
• ISSN: 1423-0127; 1021-7770; 1423-0127
• DOI: 10.1186/s12929-024-00998-8

Cell-based immunotherapies (CBIs), notably exemplified by chimeric antigen receptor (CAR)-engineered T (CAR-T) cell therapy, have emerged as groundbreaking approaches for cancer therapy. Nevertheless, akin to various other therapeutic modalities, tumor cells employ counterstrategies to manifest immune evasion, thereby circumventing the impact of CBIs. This phenomenon is facilitated by an intricately immunosuppression entrenched within the tumor microenvironment (TME). Principal mechanisms underpinning tumor immune evasion from CBIs encompass loss of antigens, downregulation of antigen presentation, activation of immune checkpoint pathways, initiation of anti-apoptotic cascades, and induction of immune dysfunction and exhaustion. In this review, we delve into the intrinsic mechanisms underlying the capacity of tumor cells to resist CBIs and proffer prospective stratagems to navigate around these challenges.