Journal
NATURE CANCER
Volume 3, Issue 9, Pages 1123-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s43018-022-00433-7
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Funding
- National Key R&D Program of China [2020YFE0202200]
- National Natural Science Foundation of China [81988101, 91959000, 91942307, 31991171]
- Beijing Municipal Science and Technology Commission [Z201100005320014, Z211100003321005]
- Beijing Advanced Innovation Center for Genomics
- Changping Laboratory
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This study demonstrates that measuring CXCL13 expression can effectively identify precursor and terminally differentiated tumor-reactive CD8(+) T cells. CXCL13(+)CD8(+) T cells are correlated with favorable responses to ICB and the treatment increases the number of such cells.
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. Zhang and colleagues analyze single-cell data from patients treated with immunotherapy in five cancer types and find that CXCL13-expressing subsets are implicated in response to treatment in the CD8(+) and CD4(+) T cell compartments.
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