Open AccessMechanisms of immunogenic cell death and immune checkpoint blockade therapy
Author(s) -
Lin Richard A.,
Lin Jessica K.,
Lin ShiawYih
Publication year - 2021
Publication title -
the kaohsiung journal of medical sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.439
H-Index - 36
eISSN - 2410-8650
pISSN - 1607-551X
DOI - 10.1002/kjm2.12375
Subject(s) - blockade , medicine , immune checkpoint , immunogenic cell death , immunogenicity , immune system , programmed cell death , immunotherapy , immunology , t cell , cytotoxic t cell , cancer research , apoptosis , receptor , biology , biochemistry , in vitro
Immunogenic cell death (ICD) refers to a form of regulated cell death that activates adaptive immunity, forming long‐term immunological memory. Using chemotherapeutic drugs to induce ICD in cancer cells can help create an inflamed, immunogenic tumor environment, key for optimal immune checkpoint blockade (ICB) therapy response. ICB targets immune checkpoints such as cytotoxic T‐lymphocyte‐associated antigen 4 (CTLA4) and programmed death 1 (PD‐1). Durable responses and better quality of life in ICB patients compared with many other treatments has prompted additional investigation into its therapeutic potential and possible approaches, in an effort to further understand the functions of the costimulatory molecules and how new treatments may be designed. In this review, we will summarize ICD induction, including stress responses, damage‐associated molecular patterns, and various assays by which immunogenicity is evaluated in dying cells. In addition, the mechanisms and biomarkers underlying the CTLA4 and PD‐1 pathways of checkpoint blockade will be covered. Finally, we will review the synergistic effects of ICD induction combined with ICB therapy, as well as combination blockade therapies involving the use of multiple drugs.