Emerging role of immunogenic cell death in cancer immunotherapy: Advancing next-generation CAR-T cell immunotherapy by combination

Cancer Lett. 2024 Aug 28:598:217079. doi: 10.1016/j.canlet.2024.217079.

Zhaokai Zhou ¹, Yumiao Mai ², Ge Zhang ³, Yingjie Wang ², Pan Sun ², Zhaohe Jing ², Zhengrui Li ⁴, Yudi Xu ⁵, Bo Han ⁶, Jian Liu ⁷

Affiliations

1 Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
2 Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
3 Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, Henan Province Key Laboratory of Cardiac Injury and Repair, Henan Province Clinical Research Center for Cardiovascular Diseases, Zhengzhou, Henan, 450052, China.
4 Department of Oral and Maxillofacial-Head and Neck Oncology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
5 Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
6 State Key Laboratory of Southwestern Chinese Medicine Resources, Hospital of Chengdu University of Traditional Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address: [email protected].
7 Department of Pediatrics, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China. Electronic address: [email protected].

PMID: 38936505 DOI: 10.1016/j.canlet.2024.217079

Abstract

Immunogenic cell death (ICD) is a stress-driven form of regulated cell death (RCD) in which dying tumor cells' specific signaling pathways are activated to release damage-associated molecular patterns (DAMPs), leading to the robust anti-tumor immune response as well as a reversal of the tumor immune microenvironment from "cold" to "hot". Chimeric antigen receptor (CAR)-T cell therapy, as a landmark in anti-tumor immunotherapy, plays a formidable role in hematologic malignancies but falls short in solid tumors. The Gordian knot of CAR-T cells for solid tumors includes but is not limited to, tumor antigen heterogeneity or absence, physical and immune barriers of tumors. The combination of ICD induction therapy and CAR-T cell immunotherapy is expected to promote the intensive use of CAR-T cell in solid tumors. In this review, we summarize the characteristics of ICD, stress-responsive mechanism, and the synergistic effect of various ICD-based therapies with CAR-T cells to effectively improve anti-tumor capacity.

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