P8.02Overexpression of PD-1 and PD-L1 in renal cell carcinoma is associated with poor prognosis in metastatic patients treated with sunitinib.
Résumé
Anti vascular growth epithelial factor (VEGF) therapies are currently used in first line of metastatic clear cell renal cell carcinoma (ccRCC), but some patients are inherently resistant to these treatments. Immunotherapy based on disruption of immune checkpoints, such as Programmed Death 1 (PD-1) and Programmed Death Ligand 1 (PD-L1), has been showed promising results. PD-1 and PD-L1 are mainly expressed by T-Cells and tumor cells respectively. Interaction between PD-1 and PD-L1 down-regulates antitumor activity and could be involved in resistance to anti-VEGF therapies. This study assessed PD-1 and PD-L1 expressions in primary ccRCC of metastatic patients with sunitinib first-line treatment and its correlation with clinical outcomes. Formalin-fixed paraffin samples were obtained from primary ccRCC before any systemic treatment. Prognostic pathological criteria and clinical data were collected with a median follow up of 27 months after introduction of sunitinib. PD-1 and PD-L1 expressions were evaluated by immunohistochemistry on the most inflammatory and the highest Fuhrman nuclear grade areas respectively, considering tumor heterogeneity. Kaplan Meier survival curves were compared by log rank test. PD-1 and PD-L1 were considered overexpressed when at least a moderate to marked density of positive immune cells and at least 30% of tumor cells were positive with moderate to strong membranous staining intensity, respectively. Overexpression of both PD-1 and PD-L1 was observed in a subgroup of 17/47 primary ccRCC (36%). Patients in this subgroup compared to others had a worse progression free survival (p = 0.001) with medians of 9 months and 14 months respectively. Even if statistical significance was not reached, there was also a trend toward a worse median overall survival (18 months versus 32). This is the first study to assess the PD-1 and PD-L1 expressions in primary ccRCC of metastatic patients with sunitinib first-line treatment. The subgroup with both PD-1 and PD-L1 overexpression should be individualized as having a peculiar immune phenotype. These patients experienced poor prognosis when treated by sunitinib and may be good candidates from anti-PD-1 or anti-PD-L1 immunotherapies.