Objective: The programmed death-1/programmed death-1 ligands (PD-1/PD-Ls) pathway is critical for attenuating autoimmunity and maintaining T cell homeostasis. It has been suggested that PD-1/PD-Ls plays an important role in tumor evasion from host immunity. Although strong evidence supports the concept of immunosurveillance and immunoediting in colorectal cancer, the immune regulatory role of PD-1/PD-Ls pathway is not clear in colorectal cancer (CRC) patients. Here we investigated the expression of PD-1 and the soluble ligands (sPD-Ls) in blood plasma of patients with inflammatory Bowel Disease (IBD) and CRC.
Methods: Age-matched 107 health controls, 109 patients with colorectal cancer and 109 patients with IBD from West China Hospital (Chengdu, Sichuan, China.) were enrolled in the present study. The levels of PD-1 and sPD-Ls in blood plasma were analyzed by enzyme linked immunosorbent assay (ELISA). Expression of PD-L1 and PD-L2 were investigated in colorectal tissue by immunohistochemical (IHC) staining.
Results: The level of PD-1 in the plasma of the CRC patients was significantly up-regulated compared with healthy people (P=0.004), but there was no significant difference between IBD patient and healthy people. The levels of PD-1 were higher in CRC patients than in IBD patients. The levels of PD-L1 and soluble PD-L2 in peripheral blood were significantly increased in CRC patients comparing to health patients (P=0.0028 and p=0.0264, respectively). sPD-Ls were correlated with circulatory PD-1 expression in the CRC patients. These results indicated that the PD-1/PD-Ls pathway is activated in the CRC patients. However, we didn't observe significant differences either between IBD patients and healthy people or between CRC patients and IBD patients. We further confirmed that PD-L1 and PD-L2 were localized in colorectal cancer cells by IHC. In 67 CRC patients, the positive rates of PD-L1 and PD-L2 were 35.3% and 65%, respectively. In addition, expression of PD-1, PD-L1 and PD-L2 were higher in the patients with metastatic CRC compared to the patients with primary CRC.
Conclusion: The higher levels of plasma sPD-Ls may be associated with CRC and may predict CRC metastatic progression. The existence of immunosuppressive PD-1 and sPD-Ls in the circulation of CRC patients may indicate that PD-Ls suppress immune responses against CRC not only locally, but also systemically. This information will provide a novel insight into the role of PD-1/PDLs in CRC-mediated immunosuppression.
Citation Format: Jipei Du, Yao Cheng, Zhigang Mao, Shiping Liao, Yanjiang Zheng, Ji Zhang, Yufang Wang. Upregulation of soluble programmed death ligands in patients with colorectal cancer. [abstract]. In: Proceedings of the CRI-CIMT-EATI-AACR Inaugural International Cancer Immunotherapy Conference: Translating Science into Survival; September 16-19, 2015; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(1 Suppl):Abstract nr A004.
- ©2016 American Association for Cancer Research.