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Expression and Prognostic Significance of CD47–SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer
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Expression and Prognostic Significance of CD47–SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer
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Journal Article
Expression and Prognostic Significance of CD47–SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer
2021
Overview
Despite the confirmed anti-cancer effects of T-cell immune checkpoint inhibitors, in colorectal cancer (CRC) they are only effective in a small subset of patients with microsatellite-unstable tumors. Thus, therapeutics targeting other types of CRCs or tumors refractory to T-cell checkpoint inhibitors are desired. The binding of aberrantly expressed CD47 on tumor cells to signal regulatory protein-alpha (SIRPA) on macrophages allows tumor cells to evade immune destruction. Based on these observations, drugs targeting the macrophage checkpoint have been developed with the expectation of anti-cancer effects against T-cell immune checkpoint inhibitor-refractory tumors. In the present study, 269 primary CRCs were evaluated immunohistochemically for CD47, SIRPA, CD68, and CD163 expression to assess their predictive utility and the applicability of CD47–SIRPA axis-modulating drugs. Thirty-five percent of the lesions (95/269) displayed CD47 expression on the cytomembrane of CRC cells. CRCs contained various numbers of tumor-associated immune cells (TAIs) with SIRPA, CD68, or CD163 expression. The log-rank test revealed that patients with CD47-positive CRCs had significantly worse survival than CD47-negative patients. Multivariate Cox hazards regression analysis identified tubular-forming histology (hazard ratio (R) = 0.23), age < 70 years (HR = 0.48), and high SIRPA-positive TAI counts (HR = 0.55) as potential favorable factors. High tumor CD47 expression (HR = 1.75), lymph node metastasis (HR = 2.26), and peritoneal metastasis (HR = 5.80) were cited as potential independent risk factors. Based on our observations, CD47–SIRPA pathway-modulating therapies may be effective in patients with CRC.
Publisher
MDPI AG,MDPI
Subject
/ Antigens, Differentiation - metabolism
/ Antigens, Differentiation, Myelomonocytic - metabolism
/ Biomarkers, Tumor - metabolism
/ Colorectal Neoplasms - metabolism
/ Colorectal Neoplasms - mortality
/ Colorectal Neoplasms - pathology
/ Colorectal Neoplasms - surgery
/ Female
/ Humans
/ Intestinal Mucosa - metabolism
/ Intestinal Mucosa - pathology
/ Male
/ Proteins
/ Receptors, Cell Surface - metabolism
/ Receptors, Immunologic - metabolism
/ Tumors
