Related Experiment Video
Updated: Nov 10, 2025
Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer
Published on: March 14, 2019
Expression and Prognostic Significance of CD47-SIRPA Macrophage Checkpoint Molecules in Colorectal Cancer
Akane Sugimura-Nagata1, Akira Koshino1, Satoshi Inoue1
1Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute 480-1195, Japan.
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.
Insights
Colorectal cancer (CRC) patients with CD47-positive tumors show worse survival. Targeting the CD47-SIRPA pathway may offer new therapeutic options for CRC, especially for tumors resistant to current treatments.
Area of Science:
- Immunology
- Oncology
- Pathology
Background:
- T-cell immune checkpoint inhibitors show limited efficacy in colorectal cancer (CRC), primarily benefiting microsatellite-unstable tumors.
- Tumor cells can evade immune destruction by binding CD47 to signal regulatory protein-alpha (SIRPA) on macrophages.
- There is a need for novel therapeutics targeting other CRC subtypes or those refractory to T-cell checkpoint inhibitors.
Purpose of the Study:
- To evaluate the expression of CD47, SIRPA, CD68, and CD163 in primary colorectal cancers (CRCs).
- To assess the predictive utility of these markers for patient survival.
- To determine the applicability of CD47-SIRPA axis-modulating drugs in CRC treatment.
Main Methods:
- Immunohistochemical evaluation of CD47, SIRPA, CD68, and CD163 in 269 primary CRCs.
- Log-rank test and multivariate Cox hazards regression analysis to assess survival outcomes and risk factors.
Main Results:
- CD47 was expressed on the cytomembrane of CRC cells in 35% of cases.
- Patients with CD47-positive CRCs exhibited significantly worse survival compared to CD47-negative patients.
- High tumor CD47 expression, lymph node metastasis, and peritoneal metastasis were identified as independent risk factors for poor survival.
Conclusions:
- CD47-SIRPA pathway-modulating therapies hold potential efficacy for colorectal cancer patients.
- Tumor-associated immune cell (TAI) counts expressing SIRPA, CD68, or CD163, along with histological features and patient age, influence survival outcomes.
