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

Yan-Ruide Li; Tyler Halladay; Lili Yang

doi:10.1186/s12929-024-00998-8

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

J Biomed Sci. 2024 Jan 12;31(1):5. doi: 10.1186/s12929-024-00998-8.

Authors

Yan-Ruide Li^#¹, Tyler Halladay^#², Lili Yang^{3

4

5

6}

Affiliations

¹ Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA. charlie.li@ucla.edu.
² Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
³ Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, 90095, USA. liliyang@ucla.edu.
⁴ Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, 90095, USA. liliyang@ucla.edu.
⁵ Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA. liliyang@ucla.edu.
⁶ Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, 90095, USA. liliyang@ucla.edu.

^# Contributed equally.

Abstract

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.

Keywords: CAR-engineered T (CAR-T) cell therapy; Cell-based immunotherapies (CBIs); Chimeric antigen receptor (CAR); Immune checkpoint proteins; Immune evasion; Tumor heterogeneity; Tumor microenvironment (TME).

Publication types

Review

MeSH terms

Humans
Immune Evasion
Immunotherapy
Immunotherapy, Adoptive
Neoplasms* / therapy
Prospective Studies
Receptors, Chimeric Antigen* / metabolism
Tumor Microenvironment

Substances

Receptors, Chimeric Antigen

Abstract

Publication types

MeSH terms

Substances

Grants and funding