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Multiplexed Immunofluorescence Imaging Reveals an Immune Rich Tumor Microenvironment in Mucinous Rectal Cancer Characterized by Increased Lymphocyte Infiltration and Enhanced PD-1 Expression.

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BACKGROUND Mucinous rectal cancer is associated with a higher incidence of microsatellite instability, and a poorer response to neoadjuvant chemoradiotherapy compared to other subtypes of rectal adenocarcinoma. Immune checkpoint inhibitors… Click to show full abstract

BACKGROUND Mucinous rectal cancer is associated with a higher incidence of microsatellite instability, and a poorer response to neoadjuvant chemoradiotherapy compared to other subtypes of rectal adenocarcinoma. Immune checkpoint inhibitors are an emerging family of anti-cancer therapeutics associated with highly variable outcomes in colorectal cancer. Though the immune landscape of mucinous rectal cancer has not been fully explored, the presence of mucin is thought to act as a barrier preventing immune cell infiltration. OBJECTIVE The aim of this study was to determine the immune properties of mucinous rectal cancer and investigate the degree of lymphocyte infiltration in this cohort. DESIGN This is a retrospective cohort study which involved, multiplexed immunofluorescence staining of tumor microarrays. SETTINGS Samples originated from a single university teaching hospital. PATIENTS Our cohort included 15 cases of mucinous and 43 cases of non-mucinous rectal cancer. MAIN OUTCOME MEASURES Immune cells were classified and quantified. Immune cell counts were compared between mucinous and non-mucinous cohorts. Immune marker expression within tumor epithelial tissue was evaluated to determine degree of lymphocyte infiltration. RESULTS Cytotoxic (p = 0.022), and regulatory T-cells (p = 0.010) were found to be overrepresented in the mucinous cohort compared to the non-mucinous group. PD-1 expression was also found to be significantly greater in the mucinous group (p = 0.001). CD3 (p = 0.001) and CD8 (p = 0.054) expression within tumor epithelium was also higher in the mucinous group, suggesting adequate immune infiltration despite the presence of mucin. Microsatellite instability status was not found to be a predictor of immune marker expression in our analysis. LIMITATIONS The relatively small size of the cohort. CONCLUSION Mucinous rectal cancer is associated with an immune rich tumor microenvironment, which was not associated with microsatellite instability status. See Video Abstract at http://links.lww.com/DCR/C65.

Keywords: infiltration; mucinous rectal; expression; rectal cancer; tumor; cancer

Journal Title: Diseases of the colon and rectum
Year Published: 2022

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