2019 ASCO-SITC Symposium: Regulatory T Cells and Treatment Resistance in Head/Neck Cancer
Posted: Friday, March 8, 2019
Research recently presented at the 2019 American Society of Clinical Oncology–Society for Immunotherapy of Cancer (ASCO-SITC) Immuno-Oncology Symposium (Abstract 70) found that infiltration of regulatory T cells (Tregs) led to improved outcomes by mediating radiotherapy resistance in patients with head and neck squamous cell carcinoma.
“Targeted depletion of Tregs represents an important mechanism of sensitizing tumors to [radiotherapy],” concluded Sana Karam, MD, PhD, of the University of Colorado Denver, and colleagues. “Our data support the design of clinical trials integrating targeted Treg inhibitors in the standard of care for cancer patients receiving [radiotherapy].”
Researchers treated mice with Treg inhibitors anti–CTLA-4, anti-CD25, and/or anti–PD-L1, in isolation as well as combined with radiotherapy. Concurrent anti-CD25 and radiotherapy resulted in a significant delay in tumor growth, increased T-cell cytotoxicity, decreased Tregs, and improved survival. Anti–CTLA-4 treatment, however, did not alter survival or tumor growth.
When combined with radiotherapy, Treg depletion caused a rise in CD8 and CD4 T cells; it also caused a change in immune cell populations by increasing M1 macrophages and decreasing M2 macrophages as well as myeloid-derived suppressor cells. Response and resistance to treatment were determined by RNA sequencing. Phenotypic and functional changes in T-cell populations were assessed via flow cytometry. A multiplex enzyme-linked immunosorbent assay was used to measure cytokines.
Disclosure: The study authors’ disclosure information may be found at coi.asco.org.