Emerging evidence in preclinical models demonstrates that antitumor immunity is not equivalent between males and females. However, more investigation in patients and across a wider range of cancer types is needed to fully understand sex as a variable in tumor immune responses. We investigated differences in T-cell responses between male and female patients with lung cancer by performing sex-based analysis of single cell transcriptomic datasets. We found that the transcript encoding CXC motif chemokine ligand 13 (CXCL13), which has recently been shown to correlate with T-cell tumor specificity, is expressed at greater levels in T cells isolated from female compared with male patients. Furthermore, increased CXCL13 expression was associated with response to PD1–targeting immunotherapy in female but not male patients. These findings suggest that there are sex-based differences in T-cell function required for response to anti–PD1 therapy in lung cancer that may need to be considered during patient treatment decisions.

Synopsis: Authors identify sex differences in T-cell CXCL13 expression and its association with immunotherapy response, suggesting male and female tumor microenvironments have unique functional requirements for effective antitumor T-cell responses, and patient sex should be included in therapy decisions.

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