IMMUNE TUMOR MICROENVIRONMENT (I-TME) ANALYSES IN METASTATIC RENAL CELL CARCINOMA (MRCC) PATIENTS (PTS) TREATED WITH SECOND LINE NIVOLUMAB: RESULTS FROM THE MEET-URO 18 STUDY

Background: To date, there are not well-established prognostic and predictive biomarkers able to predict response to immunotherapy for mRCC patients. Within the multicentric Meet-URO 18 study, we assessed the I-TME in mRCC pts treated with =2nd line nivolumab. Methods: Immunohistochemistry (IHC) analyses were performed on the primary tumor or the metastases assessing histology, grading and T-lineage (CD3, CD4, CD8, CD8/CD4 ratio, peritumoral T cells), macrophages (CD68) and granulocytes (CD15). Phosphorylated mTOR (ph-mTOR), CD56 and PD-L1 (SP263) expression on tumor cells were also assessed. Receiver operating curves (ROC) based on responses were used to identify cut-off values of IHC parameters. Patients were dichotomized in responders versus non responders according to progression-free survival (⩾ 12 vs ⩽ 3 months, respectively). Differences between the two pts groups were reported as odds ratios (OR) with the 95% CI and considered statistically significant with a p value of < 0.05. Results: Overall, 116 tumoral tissues (59% primary tumors, 41% metastases) were evaluated with responders (N = 55) presenting lower expression of CD4 and higher levels of ph-mTOR and CD56. Responders tended to have higher CD3 expression (⩾40: 73% vs 56%, p=0.059) and CD8/CD4 ratio (median 1.74 vs 1.20, p=0.084). Non responders (N = 61) presented with clear cell histology (CCRCC) and higher grading. Significant results are summarized in Table 1. Conclusions: In our study, responders to nivolumab were characterized by high expression of CD56, low levels of regulatory CD4 cells and other histologies than clear cell carcinoma. Phosphorylated mTOR could represent a new biomarker for immunotherapies to further investigate. Gene signature analyses are planned to integrate IHC analyses.