Single-cell meta-analyses reveal responses of tumor-reactive CXCL13+ T cells to immune-checkpoint blockade

B Liu, Y Zhang, D Wang, X Hu, Z Zhang - Nature Cancer, 2022 - nature.com
Nature Cancer, 2022nature.com
Immune-checkpoint blockade (ICB) therapies represent a paradigm shift in the treatment of
human cancers; however, it remains incompletely understood how tumor-reactive T cells
respond to ICB across tumor types. Here, we demonstrate that measuring CXCL13
expression could effectively identify both precursor and terminally differentiated tumor-
reactive CD8+ T cells within tumors. Applying this approach, we performed meta-analyses of
published single-cell data for CXCL13+ CD8+ T cells in 225 samples from 102 patients …
Abstract
Immune-checkpoint blockade (ICB) therapies represent a paradigm shift in the treatment of human cancers; however, it remains incompletely understood how tumor-reactive T cells respond to ICB across tumor types. Here, we demonstrate that measuring CXCL13 expression could effectively identify both precursor and terminally differentiated tumor-reactive CD8+ T cells within tumors. Applying this approach, we performed meta-analyses of published single-cell data for CXCL13+CD8+ T cells in 225 samples from 102 patients treated with ICB across five cancer types. We found that CXCL13+CD8+ T cells were correlated with favorable responses to ICB, and the treatment further increased such cells in responsive tumors. In addition, CXCL13+ tumor-reactive subsets exhibited variable responses to ICB in distinct contexts, likely due to different degrees of exhaustion-related immunosuppression. Our integrated analyses provide insights into mechanisms underlying ICB and suggest that bolstering precursor tumor-reactive CD8+ T cells might provide an effective therapeutic approach to improve cancer treatment.
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