Preclinical Rationale and Clinical Considerations for Radiotherapy Plus Immunotherapy: Going Beyond Local Control.
The use of radiation for cancer therapy has expanded and sparked interest in possible synergistic effects by combining it with current immunotherapies. In this review, we present a case of a patient who responded to programmed cell death 1 (PD1) blockade and radiation therapy and discuss possible mechanisms. We provide background on the blockade of the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and PD1 checkpoints and highlight future immune-based therapies that may synergize with radiation, including cytosine-phosphate-guanine vaccines, OX40 agonists, CD40 agonists, regulatory T-cell depletion, and metabolic "rewiring" of cancer cells. Clinical considerations are noted for combining radiation with immunotherapies to extend the benefit of immunotherapy to more patients. New trials are needed to appropriately investigate the best sequencing and radiation dose to prime an immune response and to identify predictive biomarkers of such responses.
From the *Department of Experimental Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX; †Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, IA; and ‡Department of Radiation Oncology, University of Texas MD Anderson Cancer Center; and §Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX.
Jonathan E
JE
Schoenhals
Steven N
SN
Seyedin
Chad
C
Tang
Maria A
MA
Cortez
Sharareh
S
Niknam
Efrosini
E
Tsouko
Joe Y
JY
Chang
Stephen M
SM
Hahn
James W
JW
Welsh
D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D003131:Combined Modality Therapy; D006801:Humans; D056747:Immunomodulation / Q000187:drug effects; D007167:Immunotherapy / Q000379:methods; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009369:Neoplasms / Q000175:diagnosis / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D011878:Radiotherapy / Q000379:methods; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor