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

Recent 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 type...

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Published in:Frontiers in immunology 2023-05, Vol.14, p.1162669-1162669
Main Authors: Bowen, Charles M, Deng, Nan, Reyes-Uribe, Laura, Parra, Edwin Roger, Rocha, Pedro, Solis, Luisa M, Wistuba, Ignacio I, Sepeda, Valerie O, Vornik, Lana, Perloff, Marjorie, Szabo, Eva, Umar, Asad, Sinha, Krishna M, Brown, Powel H, Vilar, Eduardo
Format: Article
Language:English
Subjects:
Antineoplastic Agents
bioinformactics
cancer prevention
Cancer Vaccines
Chemoprevention
Colorectal Neoplasms, Hereditary Nonpolyposis
Humans
image mass cytometry
Immunology
immunoprevention
Immunotherapy
Intestinal Mucosa
Lymphocytes
Lynch Syndrome (hereditary nonpolyposis colorectal cancer)
Naproxen - pharmacology
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Summary:Recent 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. Normal 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. Using 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. Our 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.
ISSN:1664-3224
1664-3224
DOI:10.3389/fimmu.2023.1162669