Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer.

Kašíková, L.; Raková, J.; Hensler, M.; Láníčková, T.; Tománková, J.; Pasulka, J.; Drozenová, J.; Mojžíšová, K.; Fialová, A.; Vošahlíková, Š.; Laco, J.; Ryška, A.; Dundr, P.; Kocián, R.; Brtnický, T.; Skapa, P.; Čapková, L.; Kovář, Marek; Procházka, Jan; Práznovec, I.; Koblížek, V.; Tasková, A.; Tanaka, H.; Lischke, R.; Mendez, F. C.; Vachtenheim, J. J.; Heinzelmann-Schwarz, V.; Jacob, F.; McNeish, I. A.; Halaška, M. J.; Rob, L.; Cibula, D.; Orsulic, S.; Galluzzi, L.; Spíšek, R.; Fučíková, J.

doi:https://dx.doi.org/10.1038/s41467-024-46873-w

Number of the records: 1

Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer.

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SYSNO ASEP	0584603
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Ostatní články
Title	Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer.
Author(s)	Kašíková, L. (CZ) Raková, J. (CZ) Hensler, M. (CZ) Láníčková, T. (CZ) Tománková, J. (CZ) Pasulka, J. (CZ) Drozenová, J. (CZ) Mojžíšová, K. (CZ) Fialová, A. (CZ) Vošahlíková, Š. (CZ) Laco, J. (CZ) Ryška, A. (CZ) Dundr, P. (CZ) Kocián, R. (CZ) Brtnický, T. (CZ) Skapa, P. (CZ) Čapková, L. (CZ) Kovář, Marek (MBU-M)_{RID, ORCID} Procházka, Jan (UMG-J)_ORCID Práznovec, I. (CZ) Koblížek, V. (CZ) Tasková, A. (CZ) Tanaka, H. (US) Lischke, R. (CZ) Mendez, F. C. (CZ) Vachtenheim, J. J. (CZ) Heinzelmann-Schwarz, V. (CH) Jacob, F. (CH) McNeish, I. A. (GB) Halaška, M. J. (CZ) Rob, L. (CZ) Cibula, D. (CZ) Orsulic, S. (US) Galluzzi, L. (US) Spíšek, R. (CZ) Fučíková, J. (CZ)
Source Title	Nature Communications. - : Nature Publishing Group Roč. 15, č. 1 (2024), s. 2528
Number of pages	19 s.
Language	eng - English
Country	US - United States
Keywords	lymphoid structures ; B cells ; T cell ; ovarian cancer
OECD category	Immunology
R&D Projects	LX22NPO5102 GA MŠMT - Ministry of Education, Youth and Sports (MEYS)
Method of publishing	Open access
Institutional support	MBU-M - RVO:61388971 ; UMG-J - RVO:68378050
DOI	10.1038/s41467-024-46873-w
Annotation	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.
Workplace	Institute of Microbiology
Contact	Eliška Spurná, eliska.spurna@biomed.cas.cz, Tel.: 241 062 231
Year of Publishing	2025
Electronic address	https://www.nature.com/articles/s41467-024-46873-w

Number of the records: 1