Naproxen chemoprevention induces proliferation of cytotoxic lymphocytes in Lynch Syndrome colorectal mucosa

Frontiers in Immunology

Immunology

Powel H. Brown¹  Krishna M. Sinha¹  Charles M. Bowen¹  Lana Vornik¹  Laura Reyes-Uribe¹  Nan Deng¹  Valerie O. Sepeda¹  Eduardo Vilar²  Marjorie Perloff³  Asad Umar³  Eva Szabo³  Luisa M. Solis⁴  Edwin Roger Parra⁴  Ignacio I. Wistuba⁴  Pedro Rocha⁴ 

[1] Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Clinical Cancer Genetics Program, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;Division of Cancer Prevention, National Cancer Institute, Bethesda, MD, United States;Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States;

关键词: Lynch Syndrome (hereditary nonpolyposis colorectal cancer);    immunoprevention;    image mass cytometry;    bioinformactics;    cancer prevention;   

DOI  :  10.3389/fimmu.2023.1162669

 received in 2023-02-09, accepted in 2023-04-20,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundRecent clinical trial data from Lynch Syndrome (LS) carriers demonstrated that naproxen administered for 6-months is a safe primary chemoprevention that promotes activation of different resident immune cell types without increasing lymphoid cellularity. While intriguing, the precise immune cell types enriched by naproxen remained unanswered. Here, we have utilized cutting-edge technology to elucidate the immune cell types activated by naproxen in mucosal tissue of LS patients.MethodsNormal colorectal mucosa samples (pre- and post-treatment) from a subset of patients enrolled in the randomized and placebo-controlled ‘Naproxen Study’ were obtained and subjected to a tissue microarray for image mass cytometry (IMC) analysis. IMC data was processed using tissue segmentation and functional markers to ascertain cell type abundance. Computational outputs were then used to quantitatively compare immune cell abundance in pre- and post-naproxen specimens.ResultsUsing data-driven exploration, unsupervised clustering identified four populations of immune cell types with statistically significant changes between treatment and control groups. These four populations collectively describe a unique cell population of proliferating lymphocytes within mucosal samples from LS patients exposed to naproxen.ConclusionsOur findings show that daily exposure of naproxen promotes T-cell proliferation in the colonic mucosa, which paves way for developing combination of immunoprevention strategies including naproxen for LS patients.

【 授权许可】

Unknown   
Copyright © 2023 Bowen, Deng, Reyes-Uribe, Parra, Rocha, Solis, Wistuba, Sepeda, Vornik, Perloff, Szabo, Umar, Sinha, Brown and Vilar