TY - JOUR
T1 - A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer
AU - Workel, Hagma H
AU - Lubbers, Joyce M
AU - Arnold, Roland
AU - Prins, Thalina M
AU - van der Vlies, Pieter
AU - de Lange, Kim
AU - Bosse, Tjalling
AU - van Gool, Inge C
AU - Eggink, Florine A
AU - Wouters, Maartje C A
AU - Komdeur, Fenne L
AU - van der Slikke, Elisabeth C
AU - Creutzberg, Carien L
AU - Kol, Arjan
AU - Plat, Annechien
AU - Glaire, Mark
AU - Church, David N
AU - Nijman, Hans W
AU - de Bruyn, Marco
N1 - ©2019 American Association for Cancer Research.
PY - 2019/5/1
Y1 - 2019/5/1
N2 - 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 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 noncanonical 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.
AB - 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 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 noncanonical 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.
KW - Antigens, CD/immunology
KW - Antigens, Neoplasm/immunology
KW - B-Lymphocytes/immunology
KW - CD8-Positive T-Lymphocytes/immunology
KW - Chemokine CXCL13/immunology
KW - Female
KW - Humans
KW - Integrin alpha Chains/immunology
KW - Ovarian Neoplasms/immunology
KW - Receptors, Transforming Growth Factor beta/immunology
U2 - 10.1158/2326-6066.CIR-18-0517
DO - 10.1158/2326-6066.CIR-18-0517
M3 - Article
C2 - 30872264
SN - 2326-6066
VL - 7
SP - 784
EP - 796
JO - Cancer immunology research
JF - Cancer immunology research
IS - 5
ER -
