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

0584603 - MBÚ 2025 RIV US eng J - Článek v odborném periodiku
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.
Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer.
Nature Communications. Roč. 15, č. 1 (2024), s. 2528. E-ISSN 2041-1723
Grant CEP: GA MŠMT LX22NPO5102
Institucionální podpora: RVO:61388971 ; RVO:68378050
Klíčová slova: lymphoid structures * B cells * T cell * ovarian cancer
Obor OECD: Immunology
Impakt faktor: 16.6, rok: 2022
Způsob publikování: Open access
https://www.nature.com/articles/s41467-024-46873-w

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.
Trvalý link: https://hdl.handle.net/11104/0352493