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

Soft 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...

Full description

Saved in:

Bibliographic Details
Published in:	Frontiers in immunology 2023, Vol.14, p.1230534-1230534
Main Authors:	Cruz, Sylvia M, Sholevar, Cyrus J, Judge, Sean J, Darrow, Morgan A, Iranpur, Khurshid R, Farley, Lauren E, Lammers, Marshall, Razmara, Aryana M, Dunai, Cordelia, Gingrich, Alicia A, Persky, Julia, Mori, Hidetoshi, Thorpe, Steven W, Monjazeb, Arta M, Murphy, William J, Canter, Robert J
Format:	Article
Language:	eng
Subjects:	CD8-Positive T-Lymphocytes - immunology Humans Immunology Killer Cells, Natural - immunology MHC-I natural killer cell NKp46 Prognosis Sarcoma - immunology Sarcoma - therapy Soft Tissue Neoplasms - immunology Soft Tissue Neoplasms - therapy soft tissue sarcomas spatial localization tumor microenvironment
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Soft 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. Using 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. Both intratumoral NKp46 and CD56 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
ISSN:	1664-3224