Published in:
Open Access 01-12-2018 | Research article
PD-L1/PD-1 crosstalk in colorectal cancer: are we targeting the right cells?
Published in: BMC Cancer | Issue 1/2018
Login to get accessAbstract
Background
The analysis of tumour-infiltrating immune cells within patients’ tumour samples in colorectal cancer (CRC) has become an independent predictor of patient survival. The tumour microenvironment and the immune checkpoints, such as PD-L1/PD-1, are relevant to the prognoses and also appear to be relevant for further CRC therapies.
Methods
We analysed the presence and features of the infiltrated monocyte/macrophage and lymphocyte populations in both tumour and peritumour samples from patients with CRC (n = 15).
Results
We detected a large number of CD14+ monocytes/macrophages with an alternative phenotype (CD64+CD163+) and CD4+ lymphocytes that infiltrated the tumour, but not the peritumour area. The monocytes/macrophages expressed PD-L1, whereas the lymphocytes were PD-1+; however, we did not find high PD-L1 levels in the tumour cells. Coculture of circulating naïve human monocytes/macrophages and lymphocytes with tumour cells from patients with proficient mismatch repair CRC induced both an alternative phenotype with higher expression of PD-L1 in CD14+ cells and the T-cell exhaustion phenomenon. The addition of an α-PD-1 antibody restored lymphocyte proliferation.
Conclusion
These results emphasise the interesting nature of immune checkpoint shifting therapies, which have potential clinical applications in the context of colorectal cancer.