A Transcriptionally Distinct CXCL13+CD103+CD8+ T-cell Population Is Associated with B-cell Recruitment and Neoantigen Load in Human Cancer.
Cancer Immunol Res
; 7(5): 784-796, 2019 05.
Article
in En
| MEDLINE
| ID: mdl-30872264
ABSTRACT
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 TGFß-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 TGFß upregulated CD103 and secreted CXCL13. Conversely, inhibition of TGFß 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 TGFß 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Ovarian Neoplasms
/
B-Lymphocytes
/
Antigens, CD
/
Receptors, Transforming Growth Factor beta
/
CD8-Positive T-Lymphocytes
/
Integrin alpha Chains
/
Chemokine CXCL13
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Cancer Immunol Res
Year:
2019
Type:
Article
Affiliation country:
Netherlands