Molecular determinants of immunogenic cell death elicited by radiation therapy

Claudia Galassi*, Vanessa Klapp, Takahiro Yamazaki, Lorenzo Galluzzi*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

4 Citations (Scopus)

Abstract

Cancer cells undergoing immunogenic cell death (ICD) can initiate adaptive immune responses against dead cell-associated antigens, provided that (1) said antigens are not perfectly covered by central tolerance (antigenicity), (2) cell death occurs along with the emission of immunostimulatory cytokines and damage-associated molecular patterns (DAMPs) that actively engage immune effector mechanisms (adjuvanticity), and (3) the microenvironment of dying cells is permissive for the initiation of adaptive immunity. Finally, ICD-driven immune responses can only operate and exert cytotoxic effector functions if the microenvironment of target cancer cells enables immune cell infiltration and activity. Multiple forms of radiation, including non-ionizing (ultraviolet) and ionizing radiation, elicit bona fide ICD as they increase both the antigenicity and adjuvanticity of dying cancer cells. Here, we review the molecular determinants of ICD as elicited by radiation as we critically discuss strategies to reinforce the immunogenicity of cancer cells succumbing to clinically available radiation strategies.

Original languageEnglish
Pages (from-to)20-32
JournalImmunological Reviews
Volume321
Issue number1
Early online date7 Sept 2023
DOIs
Publication statusPublished - Jan 2024

Keywords

  • ATP
  • calreticulin
  • HMGB1
  • immune checkpoint inhibitors
  • PD-L1
  • type I IFN

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