Expansion of tumor-reactive CD8⁺ T cell clonotypes occurs in the spleen in response to immune checkpoint blockade.

ABSTRACT: Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8⁺ T cell differentiation in response to chronic antigen stimulation is highly complex, and it remains unclear precisely which T cell differentiation states at which anatomic sites are critical for the response to ICB. We identified an intermediate-exhausted population in the white pulp of the spleen that underwent substantial expansion in response to ICB and gave rise to tumor-infiltrating clonotypes. Increased systemic antigen redirected differentiation of this population toward a more circulatory exhausted KLR state, whereas a lack of cross-presented tumor antigen reduced its differentiation in the spleen. An analogous population of exhausted K

SUBMITTER: Morgan DM 

PROVIDER: S-EPMC11580689 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature