Intratumoral NKp46+ natural killer cells are spatially distanced from T and MHC-I+ cells with prognostic implications in soft tissue sarcoma

Autor: Sylvia M. Cruz, Cyrus J. Sholevar, Sean J. Judge, Morgan A. Darrow, Khurshid R. Iranpur, Lauren E. Farley, Marshall Lammers, Aryana M. Razmara, Cordelia Dunai, Alicia A. Gingrich, Julia Persky, Hidetoshi Mori, Steven W. Thorpe, Arta M. Monjazeb, William J. Murphy, Robert J. Canter
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Frontiers in Immunology, Vol 14 (2023)
Druh dokumentu: article
ISSN: 1664-3224
DOI: 10.3389/fimmu.2023.1230534
Popis: IntroductionSoft tissue sarcomas (STS) are rare, heterogenous malignancies with an unmet need for novel immunotherapies. Tumor infiltrating lymphocytes (TILs) have been linked with favorable outcomes in STS patients, though the contribution of natural killer (NK) cells and spatial relationships of TILs with MHC-I expressing cells lacks detailed characterization.Experimental designUsing archived and prospectively collected specimens, we evaluated intratumoral NK cells by immunohistochemistry (IHC), flow cytometry, and immunofluorescence (IF). We assessed spatial localization of NK and T cells by multiplex IF, analyzing the effects of MHC-I expression status on NK and T cell clustering.ResultsBoth intratumoral NKp46 and CD56dim expression were associated with significantly improved overall survival (P=0.05), while higher infiltrates of CD56bright NK cells predicted a worse prognosis (P=0.05). The presence of intratumoral NK cells was inversely proportional to CD3+ T cells. Spatial analyses showed NK cells preferentially clustering close to other NK cells with sparse CD3+ T and CD8+ T cells in range (P
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