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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064211%3A_____%2F24%3AW0000064" target="_blank" >RIV/00064211:_____/24:W0000064 - isvavai.cz</a>

Result on the web

<a href="https://oadoi.org/10.1038/s41467-024-46873-w" target="_blank" >https://oadoi.org/10.1038/s41467-024-46873-w</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41467-024-46873-w" target="_blank" >10.1038/s41467-024-46873-w</a>

Result language

angličtina

Original language name

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

Original language description

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. Intratumoral tertiary lymphoid structure (TLS) density has been associated with better prognosis in several cancer types. Here the authors provide a comprehensive characterization of TLSs in patients with high-grade serous ovarian carcinoma.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30204 - Oncology

Project

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Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

NATURE COMMUNICATIONS

ISSN

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e-ISSN

2041-1723

Volume of the periodical

15

Issue of the periodical within the volume

1

Country of publishing house

DE - GERMANY

Number of pages

19

Pages from-to

-

UT code for WoS article

001190797000002

EID of the result in the Scopus database

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