A transcriptionally distinct CXCL13+CD103+CD8+ T-cell population is associated with B-cell recruitment and neoantigen load in human cancerWorkel, H. H., Lubbers, J. M., Arnold, R., Prins, T. M., van der Vlies, P., de Lange, K., Bosse, T., Van Gool, I. C., Eggink, F. A., Wouters, M. C., Komdeur, F. L., van der Slikke, E. C., Creutzberg, C. L., Kol, A., Plat, A., Glaire, M., Church, D. N., Nijman, H. W. & de Bruyn, M., May-2019, In : Cancer immunology research. 7, 5, p. 784-796 13 p.
Research output: Contribution to journal › Article › Academic › peer-review
The chemokine CXCL13 mediates recruitment of B cells to tumors and is essential for the formation of tertiary lymphoid structures (TLSs). TLSs are thought to support antitumor immunity and are associated with improved prognosis. However, it remains unknown whether TLSs are formed in response to the general inflammatory character of the tumor microenvironment, or rather, are induced by (neo)antigen-specific adaptive immunity. We here report on the finding that the transforming growth factor beta (TGFβ)-dependent CD103+CD8+ tumor-infiltrating T-cell (TIL) subpopulation expressed and produced CXCL13. Accordingly, CD8+ T cells from peripheral blood activated in the presence of TGFβ upregulated CD103 and secreted CXCL13. Conversely, inhibition of TGFβ receptor signaling abrogated CXCL13 production. CXCL13+CD103+CD8+ TILs correlated with B-cell recruitment, TLSs, and neoantigen burden in six cohorts of human tumors. Altogether, our findings indicated that TGFβ plays a non-canonical role in coordinating immune responses against human tumors and suggest a potential role for CXCL13+CD103+CD8+ TILs in mediating B-cell recruitment and TLS formation in human tumors.
|Number of pages||13|
|Journal||Cancer immunology research|
|Publication status||Published - May-2019|