INVITED REVIEW
Molecular determinants of immunogenic cell death elicited by radiation therapy
Claudia Galassi,
Vanessa Klapp,
Takahiro Yamazaki,
Lorenzo Galluzzi,
Corresponding Author
Claudia Galassi
Department of Radiation Oncology, Weill Cornell Medical College, New York, New York, USA
Correspondence
Claudia Galassi and Lorenzo Galluzzi, Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Email: [email protected] and [email protected]
Search for more papers by this authorVanessa Klapp
Tumor Stroma Interactions, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg
Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Search for more papers by this authorTakahiro Yamazaki
Department of Radiation Oncology, Weill Cornell Medical College, New York, New York, USA
Search for more papers by this authorCorresponding Author
Lorenzo Galluzzi
Department of Radiation Oncology, Weill Cornell Medical College, New York, New York, USA
Sandra and Edward Meyer Cancer Center, New York, New York, USA
Caryl and Israel Englander Institute for Precision Medicine, New York, New York, USA
Correspondence
Claudia Galassi and Lorenzo Galluzzi, Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Email: [email protected] and [email protected]
Search for more papers by this authorClaudia Galassi,
Vanessa Klapp,
Takahiro Yamazaki,
Lorenzo Galluzzi,
Corresponding Author
Claudia Galassi
Department of Radiation Oncology, Weill Cornell Medical College, New York, New York, USA
Correspondence
Claudia Galassi and Lorenzo Galluzzi, Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Email: [email protected] and [email protected]
Search for more papers by this authorVanessa Klapp
Tumor Stroma Interactions, Department of Cancer Research, Luxembourg Institute of Health, Luxembourg, Luxembourg
Faculty of Science, Technology and Medicine, University of Luxembourg, Esch-sur-Alzette, Luxembourg
Search for more papers by this authorTakahiro Yamazaki
Department of Radiation Oncology, Weill Cornell Medical College, New York, New York, USA
Search for more papers by this authorCorresponding Author
Lorenzo Galluzzi
Department of Radiation Oncology, Weill Cornell Medical College, New York, New York, USA
Sandra and Edward Meyer Cancer Center, New York, New York, USA
Caryl and Israel Englander Institute for Precision Medicine, New York, New York, USA
Correspondence
Claudia Galassi and Lorenzo Galluzzi, Department of Radiation Oncology, Weill Cornell Medical College, New York, NY, USA.
Email: [email protected] and [email protected]
Search for more papers by this authorThis article is part of a series of reviews covering Mechanisms of programmed cell death appearing in Volume 321 of Immunological Reviews.
Summary
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.
CONFLICT OF INTEREST STATEMENT
LG is/has been holding research contracts with Lytix Biopharma, Promontory and Onxeo, has received consulting/advisory honoraria from Boehringer Ingelheim, AstraZeneca, OmniSEQ, Onxeo, The Longevity Labs, Inzen, Imvax, Sotio, Promontory, Noxopharm, EduCom, and the Luke Heller TECPR2 Foundation, and holds Promontory stock options.
Open Research
DATA AVAILABILITY STATEMENT
Not applicable, review article
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