Human B Cells Mediate Innate Anti-Cancer Cytotoxicity Through Concurrent Engagement of Multiple TNF Superfamily Ligands.

Autor:	Janjic BM; UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States., Kulkarni A; UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States.; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, United States., Ferris RL; UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States.; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, United States.; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, United States., Vujanovic L; UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States.; Department of Otolaryngology, University of Pittsburgh, Pittsburgh, PA, United States., Vujanovic NL; UPMC Hillman Cancer Center, University of Pittsburgh, Pittsburgh, PA, United States.; Department of Pathology, University of Pittsburgh, Pittsburgh, PA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Mar 22; Vol. 13, pp. 837842. Date of Electronic Publication: 2022 Mar 22 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.837842
Abstrakt:	The essential innate immunity effector cells, natural killer and dendritic cells, express multiple plasma membrane-associated tumor necrosis factor (TNF) superfamily (TNFSF) ligands that, through simultaneous and synergistic engagement, mediate anti-cancer cytotoxicity. Here, we report that circulating B cells, mediators of adaptive humoral immunity, also mediate this innate anti-cancer immune mechanism. We show that resting human B cells isolated from peripheral blood induce apoptosis of, and efficiently kill a large variety of leukemia and solid tumor cell types. Single-cell RNA sequencing analyses indicate, and flow cytometry data confirm that B cells from circulation express transmembrane TNF, Fas ligand (FasL), lymphotoxin (LT) α1β2 and TNF-related apoptosis-inducing ligand (TRAIL). The cytotoxic activity can be inhibited by individual and, especially, combined blockade of the four transmembrane TNFSF ligands. B cells from tumor-bearing head and neck squamous cell carcinoma patients express lower levels of TNFSF ligands and are less cytotoxic than those isolated from healthy individuals. In conclusion, we demonstrate that B cells have the innate capacity to mediate anti-cancer cytotoxicity through concurrent activity of multiple plasma membrane-associated TNFSF ligands, that this mechanism is deficient in cancer patients and that it may be part of a general cancer immunosurveillance mechanism. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Janjic, Kulkarni, Ferris, Vujanovic and Vujanovic.)
Databáze:	MEDLINE
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