Characterization of Tumor and Immune Tumor Microenvironment of Primary Tumors and Metastatic Sites in Advanced Renal Cell Carcinoma Patients Based on Response to Nivolumab Immunotherapy: Preliminary Results from the Meet-URO 18 Study

Background: Prognostic and predictive factors for patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy are highly warranted, and the immune tumor microenvironment (I-TME) is under investigation.

Methods: The Meet-URO 18 was a multicentric retrospective study assessing the I-TME in mRCC patients treated with ≥2nd-line nivolumab, dichotomized into and according to progression-free survival (≥12 months and ≤3 months, respectively). The primary objective was to identify differential immunohistochemical (IHC) patterns between the two groups. Lymphocyte infiltration and the expressions of different proteins on tumor cells (CD56, CD15, CD68, and ph-mTOR) were analyzed. The expression of PD-L1 was also assessed.

Results: A total of 116 tumor tissue samples from 84 patients (59% were primary tumors and 41% were metastases) were evaluated. Samples from (N = 55) were significantly associated with lower expression of CD4+ T lymphocytes and higher levels of ph-mTOR and CD56+ compared with samples from (N = 61). also showed a higher CD3+ expression ( = 0.059) and CD8+/CD4+ ratio ( = 0.084). were significantly associated with a higher percentage of clear cell histology and grading.

Conclusions: Differential IHC patterns between the tumors in patients who were and to nivolumab were identified. Further investigation with genomic analyses is planned.