Gene expression analyses of immune tumor microenvironment in advanced renal cell carcinoma patients based on response to immunotherapy (Meet-URO 18 I-TME study)

Abstract

Despite many treatment strategies available for metastatic renal cell carcinoma (mRCC), predictive biomarkers of response to immunotherapy are still needed. In this context, growing efforts have been devoted to translational research, especially focusing on the immune tumor microenvironment (I-TME). The Meet-URO 18 is a multicentric retrospective study assessing the I-TME of mRCC patients receiving ≥ 2nd line nivolumab, divided into responders and non-responders according to clinical benefit [progression-free survival ≥ 12 and ≤ 3 months]. The primary objective was to identify differential immunohistochemical and molecular patterns between the two groups. We present the transcriptomic analysis performed on primary tumor tissues using a custom NanoString panel of 66 genes from the D’Costa et al. signature, grouped into angiogenesis, T-effector response, tumor invasion, and calcium signaling. Forty-two samples (25 responders and 17 non-responders) underwent transcriptomic analysis using the NanoString 66-gene immune-oncology panel. Hierarchical clustering recapitulated the transcriptional axes described by D’Costa et al. but did not distinguish patients by immunotherapy response. No genes were significantly differentially expressed after multiple testing correction; however, CD34 showed the strongest nominal association with responder tumors and was upregulated in this group, but did not retain statistical significance after adjustment. CD34 expression also correlated with CD8+ T-cell infiltration. Our findings confirm the applicability of the D’Costa molecular signature and identify CD34 as the strongest nominally associated transcript in responder tumors, warranting further orthogonal and prospective validation.