Tertiary lymphoid structures and B cells determine clinically relevant T cell phenotypes in ovarian cancer
Year: 2024
Type: article
Study design: Observational Study
Abstract: 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.
Source: Nature Communications
Authors: Lenka Kasikova, Jana Rakova, Michal Hensler, Tereza Lanickova, Jana Tomankova, Josef Pasulka, Jana Drozenova, Katerina Mojzisova, Anna Fialova, Sarka Vosahlikova, Jan Laco, Ales Ryska, Pavel Dundr, Roman Kocian, Tomas Brtnicky, Petr Skapa, Linda Capkova, Marek Kovar, Jan Prochazka, Ivan Praznovec, Vladimir Koblizek, Alice Taskova, Hisashi Tanaka, Robert Lischke, Fernando Casas Mendez, Jiri Vachtenheim, Viola Heinzelmann-Schwarz, Francis Jacob, Iain A. McNeish, Michal J. Halaska, Lukas Rob, David Cibula, Sandra Orsulic, Lorenzo Galluzzi, Radek Spisek, Jitka Fucikova
Institutions: Sotio (Czechia), Charles University, University Hospital in Motol, University Hospital Kralovske Vinohrady, University Hospital Hradec Králové, General University Hospital in Prague, Fakultní nemocnice Bulovka, Czech Academy of Sciences, Czech Academy of Sciences, Institute of Microbiology, Czech Academy of Sciences, Institute of Molecular Genetics, Czech Centre for Phenogenomics, Thomayer University Hospital, Cedars-Sinai Medical Center, University of Basel, University Hospital of Basel, Ovarian Cancer Action, Imperial College London, University of California, Los Angeles, Weill Cornell Medicine
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,790
Awards: G1118322976, Mechanisms of gene amplification in human cancers, Molecular profiling and drug prediction in ovarian cancer patients, G3220812406, Cancer-Associated Fibroblasts Alter the Composition of B cells in Solid Malignancies, G3848105304, G7185013638, G85422383, Targeting the BCL2 immune checkpoint to enhance the immunostimulatory effects of radiation in breast cancer
OpenAlex ID: W4393040331