B cell signatures and tertiary lymphoid structures contribute to outcome in head and neck squamous cell carcinoma.

Autor: Ruffin AT; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.; Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Hillman Cancer Center, Pittsburgh, PA, USA., Cillo AR; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.; Hillman Cancer Center, Pittsburgh, PA, USA., Tabib T; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Liu A; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA., Onkar S; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.; Program in Microbiology and Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.; Hillman Cancer Center, Pittsburgh, PA, USA., Kunning SR; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.; Hillman Cancer Center, Pittsburgh, PA, USA., Lampenfeld C; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.; Hillman Cancer Center, Pittsburgh, PA, USA., Atiya HI; Hillman Cancer Center, Pittsburgh, PA, USA.; Division of Hematology and Oncology, Department of Medicine, Hillman Cancer Center, Pittsburgh, PA, USA., Abecassis I; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.; Hillman Cancer Center, Pittsburgh, PA, USA., Kürten CHL; Department of Otorhinolaryngology, University Duisburg-Essen, Essen, Germany., Qi Z; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Soose R; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA., Duvvuri U; Hillman Cancer Center, Pittsburgh, PA, USA.; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., Kim S; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA., Oesterrich S; Hillman Cancer Center, Pittsburgh, PA, USA.; Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, USA.; Women's Cancer Research Center, Magee-Womens Research Institute, University of Pittsburgh, Pittsburgh, PA, USA., Lafyatis R; Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA., Coffman LG; Hillman Cancer Center, Pittsburgh, PA, USA.; Division of Hematology and Oncology, Department of Medicine, Hillman Cancer Center, Pittsburgh, PA, USA., Ferris RL; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.; Hillman Cancer Center, Pittsburgh, PA, USA.; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, USA.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Vignali DAA; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA.; Hillman Cancer Center, Pittsburgh, PA, USA.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA., Bruno TC; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA. tbruno@pitt.edu.; Tumor Microenvironment Center, Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, USA. tbruno@pitt.edu.; Hillman Cancer Center, Pittsburgh, PA, USA. tbruno@pitt.edu.; Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA, USA. tbruno@pitt.edu.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2021 Jun 07; Vol. 12 (1), pp. 3349. Date of Electronic Publication: 2021 Jun 07.
DOI: 10.1038/s41467-021-23355-x
Abstrakt: Current immunotherapy paradigms aim to reinvigorate CD8 + T cells, but the contribution of humoral immunity to antitumor immunity remains understudied. Here, we demonstrate that in head and neck squamous cell carcinoma (HNSCC) caused by human papillomavirus infection (HPV + ), patients have transcriptional signatures of germinal center (GC) tumor infiltrating B cells (TIL-Bs) and spatial organization of immune cells consistent with tertiary lymphoid structures (TLS) with GCs, both of which correlate with favorable outcome. GC TIL-Bs in HPV + HNSCC are characterized by distinct waves of gene expression consistent with dark zone, light zone and a transitional state of GC B cells. Semaphorin 4a expression is enhanced on GC TIL-Bs present in TLS of HPV + HNSCC and during the differentiation of TIL-Bs. Our study suggests that therapeutics to enhance TIL-B responses in HNSCC should be prioritized in future studies to determine if they can complement current T cell mediated immunotherapies.
Databáze: MEDLINE
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