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Expression and Prognostic Significance of CD47-SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer.
- Source :
-
International journal of molecular sciences [Int J Mol Sci] 2021 Mar 07; Vol. 22 (5). Date of Electronic Publication: 2021 Mar 07. - Publication Year :
- 2021
-
Abstract
- 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.
- Subjects :
- Aged
Aged, 80 and over
Antigens, CD metabolism
Antigens, Differentiation, Myelomonocytic metabolism
Biomarkers, Tumor metabolism
Colorectal Neoplasms metabolism
Colorectal Neoplasms surgery
Female
Humans
Intestinal Mucosa metabolism
Intestinal Mucosa pathology
Macrophages metabolism
Macrophages pathology
Male
Middle Aged
Prognosis
Receptors, Cell Surface metabolism
Survival Analysis
CD163 Antigen
Antigens, Differentiation metabolism
CD47 Antigen metabolism
Colorectal Neoplasms mortality
Colorectal Neoplasms pathology
Receptors, Immunologic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1422-0067
- Volume :
- 22
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- International journal of molecular sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33799989
- Full Text :
- https://doi.org/10.3390/ijms22052690