Radiation therapy-induced remodeling of the tumor immune microenvironment.

TitleRadiation therapy-induced remodeling of the tumor immune microenvironment.
Publication TypeJournal Article
Year of Publication2022
AuthorsCharpentier M, Spada S, Van Nest SJ, Demaria S
JournalSemin Cancer Biol
IssuePt 2
Date Published2022 Nov
KeywordsAntigens, Neoplasm, Humans, Immunotherapy, Neoplasms, T-Lymphocytes, Tumor Microenvironment

The tumor immune microenvironment is a determinant of response to cancer immunotherapy and, in many cases, is prognostic for patient survival independently of the type of treatment. Radiation therapy is used in most cancer patients for its direct cytotoxic effects on malignant cells but there is increasing evidence that it also reprograms the tumor immune microenvironment. In this review we discuss the main mechanisms whereby the local inflammatory reaction induced by radiation can reset the cross-talk between the tumor and the immune system. The outcome reflects the balance between immunostimulatory signals that lead to increased tumor antigen presentation and effector T cell activation, and immunosuppressive signals that hinder radiation-induced tumor rejection. The emerging role of small extracellular vesicles (exosomes) in this process will be discussed. Overall, preclinical and early clinical findings support the hypothesis that radiation has the potential to generate an immune-permissive tumor microenvironment. An improved understanding of the pathways involved will enable the design of more effective combinations of radiation and immunotherapy, based on a rationale integration of radiation with other interventions.

Alternate JournalSemin Cancer Biol
PubMed ID35405340
Grant ListR01 CA198533 / CA / NCI NIH HHS / United States
Related Faculty: 
Sandra Demaria, M.D.

Pathology & Laboratory Medicine 1300 York Avenue New York, NY 10065 Phone: (212) 746-6464
Surgical Pathology: (212) 746-2700