| Literature DB >> 34937729 |
Juha P Väyrynen1,2,3, Koichiro Haruki1,2,4, Mai Chan Lau2, Sara A Väyrynen1, Jeffrey A Meyerhardt1, Marios Giannakis1,5,6, Shuji Ogino7,8,5,9, Jonathan A Nowak7, Tomotaka Ugai2,8, Naohiko Akimoto2, Rong Zhong2, Melissa Zhao2, Andressa Dias Costa1, Jennifer Borowsky10, Phoenix Bell2, Yasutoshi Takashima2, Kenji Fujiyoshi2, Kota Arima2, Junko Kishikawa2, Shan-Shan Shi2, Tyler S Twombly2, Mingyang Song11,12,13, Kana Wu8,11,14, Andrew T Chan12,13,14,15, Xuehong Zhang14, Charles S Fuchs16,17,18,19.
Abstract
Although tumor-infiltrating T cells hold a beneficial prognostic role in colorectal cancer, other lymphocytic populations are less characterized. We developed a multiplexed immunofluorescence assay coupled with digital image analysis and machine learning to identify natural killer (NK) cells (NCAM1+CD3-), natural killer T-like (NKT-like) cells (NCAM1+CD3+), and T cells (NCAM1-CD3+) within the PTPRC+ (CD45+) cell population and to measure their granzyme B (GZMB; cytotoxicity marker) and FCGR3A (CD16a; NK-cell maturity marker) expression. We evaluated immune cell densities and spatial configuration in 907 incident colorectal carcinoma cases within two prospective cohort studies. We found that T cells were approximately 100 times more abundant than NK and NKT-like cells. Overall, NK cells showed high GZMB expression and were located closer to tumor cells than T and NKT-like cells. In T and NKT-like cells, GZMB expression was enriched in cells in closer proximity to tumor cells. Higher densities of both T and NKT-like cells associated with longer cancer-specific survival, independent of potential confounders (P trend < 0.0007). Higher stromal GZMB+ and FCGR3A+ NK-cell densities associated with longer cancer-specific survival (P trend < 0.003). For T and NKT-like cells, greater proximity to tumor cells associated with longer cancer-specific survival (P trend < 0.0001). These findings indicate that cytotoxic NCAM1+CD3-GZMB+ NK cells and NCAM1+CD3+ NKT-like cells are relatively rare lymphocytic populations within the colorectal cancer microenvironment and show distinct spatial configuration and associations with patient outcome. The results highlight the utility of a quantitative multimarker assay for in situ, single-cell immune biomarker evaluation and underscore the importance of spatial context for tumor microenvironment characterization. ©2021 American Association for Cancer Research.Entities:
Mesh：
Year: 2021 PMID： 34937729 PMCID： PMC8816895 DOI： 10.1158/2326-6066.CIR-21-0772
Source DB: PubMed Journal: Cancer Immunol Res ISSN： 2326-6066 Impact factor: 12.020