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Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer
L. Kasikova, J. Rakova, M. Hensler, T. Lanickova, J. Tomankova, J. Pasulka, J. Drozenova, K. Mojzisova, A. Fialova, S. Vosahlikova, J. Laco, A. Ryska, P. Dundr, R. Kocian, T. Brtnicky, P. Skapa, L. Capkova, M. Kovar, J. Prochazka, I. Praznovec,...
Jazyk angličtina Země Anglie, Velká Británie
Typ dokumentu časopisecké články
NLK
Directory of Open Access Journals
od 2015
Free Medical Journals
od 2010
Nature Open Access
od 2010-12-01
PubMed Central
od 2012
Europe PubMed Central
od 2012
ProQuest Central
od 2010-01-01
Open Access Digital Library
od 2015-01-01
Open Access Digital Library
od 2015-01-01
Medline Complete (EBSCOhost)
od 2012-11-01
Health & Medicine (ProQuest)
od 2010-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2010
Springer Nature OA/Free Journals
od 2010-12-01
- MeSH
- CD8-pozitivní T-lymfocyty MeSH
- ektopické lymfoidní struktury * MeSH
- fenotyp MeSH
- lidé MeSH
- nádorové mikroprostředí MeSH
- nádory plic * MeSH
- nádory vaječníků * patologie MeSH
- nemalobuněčný karcinom plic * MeSH
- tumor infiltrující lymfocyty MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Intratumoral tertiary lymphoid structures (TLSs) have been associated with improved outcome in various cohorts of patients with cancer, reflecting their contribution to the development of tumor-targeting immunity. Here, we demonstrate that high-grade serous ovarian carcinoma (HGSOC) contains distinct immune aggregates with varying degrees of organization and maturation. Specifically, mature TLSs (mTLS) as forming only in 16% of HGSOCs with relatively elevated tumor mutational burden (TMB) are associated with an increased intratumoral density of CD8+ effector T (TEFF) cells and TIM3+PD1+, hence poorly immune checkpoint inhibitor (ICI)-sensitive, CD8+ T cells. Conversely, CD8+ T cells from immunologically hot tumors like non-small cell lung carcinoma (NSCLC) are enriched in ICI-responsive TCF1+ PD1+ T cells. Spatial B-cell profiling identifies patterns of in situ maturation and differentiation associated with mTLSs. Moreover, B-cell depletion promotes signs of a dysfunctional CD8+ T cell compartment among tumor-infiltrating lymphocytes from freshly isolated HGSOC and NSCLC biopsies. Taken together, our data demonstrate that - at odds with NSCLC - HGSOC is associated with a low density of follicular helper T cells and thus develops a limited number of mTLS that might be insufficient to preserve a ICI-sensitive TCF1+PD1+ CD8+ T cell phenotype. These findings point to key quantitative and qualitative differences between mTLSs in ICI-responsive vs ICI-irresponsive neoplasms that may guide the development of alternative immunotherapies for patients with HGSOC.
Caryl and Israel Englander Institute for Precision Medicine New York NY USA
Department of Pneumology University Hospital Hradec Kralove Hradec Kralove Czech Republic
Department of Radiation Oncology Weill Cornell Medical College New York NY USA
Sandra and Edward Meyer Cancer Center New York NY USA
Citace poskytuje Crossref.org
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