Analyzing ovarian tumor mRNA, Workel and Lubbers et al. identified a distinct CD103+CD8+ T cell population with an activated, exhausted phenotype and high CXCL13 expression. Peripheral blood CD8+ T cells activated in the presence of TGFβ expressed CD103 and secreted CXCL13. In TCGA, higher predicted neoantigen load and CD103+ infiltrate in uterine cancers correlated with B cell and tertiary lymphoid structure (TLS)-associated genes, and CXCL13+CD103+ T cell and TLS genes correlated across various cancers. CXCL13+CD103+ T cells associated with improved survival even in endometrial tumors with low predicted neoantigen load.
Contributed by Alex Najibi
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 (TGFbeta)-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 TGFbeta upregulated CD103 and secreted CXCL13. Conversely, inhibition of TGFbeta 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 TGFbeta 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.
Author Info: (1) Obstetrics and gynecology, University Medical Center Groningen. (2) Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen. (3) Institute of Ca
Author Info: (1) Obstetrics and gynecology, University Medical Center Groningen. (2) Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen. (3) Institute of Cancer and Genomic Sciences, University of Birmingham. (4) Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen. (5) Genetics, University of Groningen, University Medical Center Groningen. (6) Genetics, University Medical Center Groningen. (7) Pathology, Leiden University Medical Center. (8) Department of Pathology, Leiden University Medical Center. (9) Department of Obstetrics and Gynecology, University of Groningen. (10) Deeley Research Centre, BC Cancer. (11) Obstetrics and gynecology, University Medical Center Groningen. (12) Obstetrics and gynecology, University Medical Center Groningen. (13) Dept of Radiation Oncology, Leiden University Medical Center. (14) Medical Oncology, University Medical Center Groningen. (15) Obstetrics and gynecology, University Medical Center Groningen. (16) Molecular and Population Genetics Laboratory, University of Oxford, The Wellcome Trust Centre for Human Genetics and Oxford Cancer Centre. (17) Wellcome Centre for Human Genetics, University of Oxford. (18) Department of Obstetrics and Gynecology, University of Groningen. (19) Department of Obstetrics and Gynecology, University of Groningen, University Medical Center Groningen m.de.bruyn@umcg.nl.
