Expansion of circulating stem-like CD8⁺ T cells by adding CD122-directed IL-2 complexes to radiation and anti-PD1 therapies in mice.

ABSTRACT: Combination of radiation therapy (RT) with immune checkpoint blockade can enhance systemic anti-tumor T cell responses. Here, using two mouse tumor models, we demonstrate that adding long-acting CD122-directed IL-2 complexes (IL-2c) to RT/anti-PD1 further increases tumor-specific CD8⁺ T cell numbers. The highest increase (>50-fold) is found in the blood circulation. Compartmental analysis of exhausted T cell subsets shows that primarily undifferentiated, stem-like, tumor-specific CD8⁺ T cells expand in the blood; these cells express the chemokine receptor CXCR3, which is required for migration into tumors. In tumor tissue, effector-like but not terminally differentiated exhausted CD8⁺ T cells increase. Consistent with the surge in tumor-specific CD8^+</

SUBMITTER: Onyshchenko K 

PROVIDER: S-EPMC10097749 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature