The signature of a T-cell response to KSHV persists across space and time in individuals with epidemic and endemic KS from Uganda.

Autor:	Ravishankar S; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, United States., Towlerton AMH; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.; Hutchinson Centre Research Institute - Uganda, Kampala, Uganda., Mooka P; Hutchinson Centre Research Institute - Uganda, Kampala, Uganda., Kafeero J; Hutchinson Centre Research Institute - Uganda, Kampala, Uganda., Coffey DG; Division of Myeloma, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United States., Aicher LD; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, United States., Mubiru KR; Hutchinson Centre Research Institute - Uganda, Kampala, Uganda., Okoche L; Hutchinson Centre Research Institute - Uganda, Kampala, Uganda., Atwinirembabazi P; Hutchinson Centre Research Institute - Uganda, Kampala, Uganda., Okonye J; Hutchinson Centre Research Institute - Uganda, Kampala, Uganda., Phipps WT; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.; Department of Medicine, University of Washington, Seattle, WA, United States., Warren EH; Translational Science and Therapeutics Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.; Department of Medicine, University of Washington, Seattle, WA, United States.; Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2024 Feb 08. Date of Electronic Publication: 2024 Feb 08.
DOI:	10.1101/2024.02.06.579223
Abstrakt:	Inadequate T-cell control of Kaposi sarcoma-associated herpesvirus (KSHV) infection predisposes to development of Kaposi sarcoma (KS), but little is known about the T-cell response to KSHV. Postulating that KS tumors contain abundant KSHV-specific T-cells, we performed transcriptional profiling and T-cell receptor (TCR) repertoire analysis of tumor biopsies from 144 Ugandan adults with KS. We show that CD8 + T-cells and M2-polarized macrophages dominate the tumor micro-environment (TME). The TCR repertoire of KS tumor infiltrating lymphocytes (TIL) is shared across non-contiguous tumors and persists across time. Clusters of T-cells with predicted shared specificity for uncharacterized antigens, potentially encoded by KSHV, comprise ~25% of KS TIL, and are shared across tumors from different time points and individuals. Single-cell RNA-sequencing of blood identifies a non-proliferating effector memory phenotype and captured the TCRs in 14,698 putative KSHV-specific T-cells. These results suggest that a polyspecific KSHV-specific T-cell response inhibited by M2 macrophages exists within the KS TME, and provide a foundation for studies to define its specificity at a large scale. Competing Interests: Conflict of Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be constructed as a potential conflict of interest.
Databáze:	MEDLINE
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