Single-cell analysis of localized prostate cancer patients links high Gleason score with an immunosuppressive profile.

Autor: Adorno Febles VR; Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA.; Department of Medicine, Manhattan Campus, VA NY Harbor Health Care System, New York, New York, USA., Hao Y; Applied Bioinformatics Laboratories, New York University Langone Health, New York, New York, USA., Ahsan A; Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA., Wu J; Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA., Qian Y; Department of Population Health, NYU Langone Health, New York, New York, USA., Zhong H; Department of Population Health, NYU Langone Health, New York, New York, USA., Loeb S; Department of Urology, New York University School of Medicine, New York, New York, USA.; Department of Urology, Manhattan Campus, VA NY Harbor Health Care System, New York, New York, USA., Makarov DV; Department of Urology, New York University School of Medicine, New York, New York, USA.; Department of Urology, Manhattan Campus, VA NY Harbor Health Care System, New York, New York, USA., Lepor H; Department of Urology, New York University School of Medicine, New York, New York, USA., Wysock J; Department of Urology, New York University School of Medicine, New York, New York, USA., Taneja SS; Department of Urology, New York University School of Medicine, New York, New York, USA., Huang WC; Department of Urology, New York University School of Medicine, New York, New York, USA., Becker DJ; Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA.; Department of Medicine, Manhattan Campus, VA NY Harbor Health Care System, New York, New York, USA., Balar AV; Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA., Melamed J; Department of Pathology, New York University School of Medicine, New York, New York, USA., Deng FM; Department of Pathology, New York University School of Medicine, New York, New York, USA., Ren Q; Department of Pathology, New York University School of Medicine, New York, New York, USA., Kufe D; Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA., Wong KK; Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA., Adeegbe DO; Department of Immunology, H. Lee Moffitt Cancer Center, Tampa, Florida, USA., Deng J; Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA., Wise DR; Department of Medicine, Laura & Isaac Perlmutter Cancer Center, NYU Langone Health, New York, New York, USA.
Jazyk: angličtina
Zdroj: The Prostate [Prostate] 2023 Jun; Vol. 83 (9), pp. 840-849. Date of Electronic Publication: 2023 Mar 29.
DOI: 10.1002/pros.24524
Abstrakt: Background: Evading immune surveillance is a hallmark for the development of multiple cancer types. Whether immune evasion contributes to the pathogenesis of high-grade prostate cancer (HGPCa) remains an area of active inquiry.
Methods: Through single-cell RNA sequencing and multicolor flow cytometry of freshly isolated prostatectomy specimens and matched peripheral blood, we aimed to characterize the tumor immune microenvironment (TME) of localized prostate cancer (PCa), including HGPCa and low-grade prostate cancer (LGPCa).
Results: HGPCa are highly infiltrated by exhausted CD8 + T cells, myeloid cells, and regulatory T cells (TRegs). These HGPCa-infiltrating CD8 + T cells expressed high levels of exhaustion markers including TIM3, TOX, TCF7, PD-1, CTLA4, TIGIT, and CXCL13. By contrast, a high ratio of activated CD8 +  effector T cells relative to TRegs and myeloid cells infiltrate the TME of LGPCa. HGPCa CD8 +  tumor-infiltrating lymphocytes (TILs) expressed more androgen receptor and prostate-specific membran antigen yet less prostate-specific antigen than the LGPCa CD8 +  TILs. The PCa TME was infiltrated by macrophages but these did not clearly cluster by M1 and M2 markers.
Conclusions: Our study reveals a suppressive TME with high levels of CD8 + T cell exhaustion in localized PCa, a finding enriched in HGPCa relative to LGPCa. These studies suggest a possible link between the clinical-pathologic risk of PCa and the associated TME. Our results have implications for our understanding of the immunologic mechanisms of PCa pathogenesis and the implementation of immunotherapy for localized PCa.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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