Expansion of Circulating Stem-like CD8 T Cells by Adding CD122-directed IL-2 Complexes to Radiation and Anti-PD1 Therapies in Mice

Overview

Journal Nat Commun

Specialty Biology

Date 2023 Apr 12

PMID 37045833

Authors

Kateryna Onyshchenko

Ren Luo

Elena Guffart

Simone Gaedicke

Anca-Ligia Grosu

Elke Firat

Gabriele Niedermann

Affiliations

Soon will be listed here.

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 T cells in blood that are migration and proliferation competent, we observe a CD8-dependent and CXCR3-dependent enhancement of the abscopal effect against distant/non-irradiated tumors and find that CD8 T cells isolated from blood after RT/anti-PD1/IL-2c triple treatment can be a rich source of tumor-specific T cells for adoptive transfers.

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