PD-L1/PD-1 crosstalk in colorectal cancer: are we targeting the right cells?
BMC Cancer
; 18(1): 945, 2018 Oct 03.
Article
in En
| MEDLINE
| ID: mdl-30285662
ABSTRACT
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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Colorectal Neoplasms
/
Signal Transduction
/
Biomarkers, Tumor
/
B7-H1 Antigen
/
Programmed Cell Death 1 Receptor
Limits:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Language:
En
Journal:
BMC Cancer
Journal subject:
NEOPLASIAS
Year:
2018
Type:
Article
Affiliation country:
Spain