Clinical significance and therapeutic potential of programmed death-1 ligand-1 and programmed death-1 ligand-2 expression in human colorectal cancer
Grimm, M.; Gasser, M.; Koenigshausen, M.; Stein, C.; Lutz, J.; Krol, S.; Thiede, A.; Heemann, U.; Waaga-Gasser, A.
Journal of Clinical Oncology 26(15_Suppl): 15005-15005
NlmCategory="UNASSIGNED">15005 Background: The negative regulatory programmed death-1/programmed death-1ligand (PD-1/PD-L) pathway in T-cell activation has been suggested to play an important role in tumor evasion from host immunity. Levels of immune cells expressing PD-1 in clinical colorectal carcinoma (CRC) tumors have not been evaluated. Thus, we investigated whether PD-1 positive T cells were expressed within CRC tumors and the expression of PD-L1 and PD-L2 in human CRC to define their clinical significance in patients' prognosis after surgery. Tissue samples from 116 patients operated between 2001 and 2005 were collected in our institution and histologically confirmed CRC were evaluated retrospectively for this study. PD-1 and PD-L gene expression was evaluated by real time quantitative PCR and the samples were immunostained. Outcome analyses were performed. The protein and the mRNA levels of determination by immunohistochemistry and real time quantitative PCR were closely correlated. PD-L expression was inversely correlated with tumor-infiltrating T lymphocytes, particularly CD8+ T cells. T cell infiltration was observed in 105 (90.5%) specimens. 93 (80.2%) specimens were PD-1+ T cells. Intratumoral PD-1+ T cells were associated with advanced tumor stage (p=0.002). Patients with PD-1+ T cells had significantly more PD-L1 tumor cell expression. Multivariate analysis indicated that PD-L positive patients and those with PD-1+ T cells had a significantly poorer prognosis than the negative patients. This was more pronounced in the advanced stage of tumor than in the early stage. These data suggest that interactions of T cells expressing PD-1 and PD-L may promote cancer progression. PD-L1 and PD-L2 status may be a new predictor of prognosis for patients with colorectal carcinoma. No significant financial relationships to disclose.