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.

Abstract

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 responders and non-responders 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 responders (N = 55) were significantly associated with lower expression of CD4+ T lymphocytes and higher levels of ph-mTOR and CD56+ compared with samples from non-responders (N = 61). Responders also showed a higher CD3+ expression (p = 0.059) and CD8+/CD4+ ratio (p = 0.084). Non-responders were significantly associated with a higher percentage of clear cell histology and grading.

CONCLUSIONS:

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

• Authors: Sara Elena Rebuzzi, Matteo Brunelli, Francesca Galuppini, Valerio Gaetano Vellone, Alessio Signori, Fabio Catalano, Alessandra Damassi, Gabriele Gaggero, Pasquale Rescigno, Marco Maruzzo, Sara Merler, Francesca Vignani, Alessia Cavo, Umberto Basso, Michele Milella, Olimpia Panepinto, Manlio Mencoboni, Marta Sbaraglia, Angelo Paolo Dei Tos, Veronica Murianni, Malvina Cremante, Miguel Angel Llaja Obispo, Michele Maffezzoli, Giuseppe Luigi Banna, Sebastiano Buti, Giuseppe Fornarini
• Journal: Cancers (Cancers (Basel)) Vol. 15 Issue 8 (Apr 21 2023) ISSN: 2072-6694 [Print] Switzerland
• PMID: 37190322 (Publication Type: Journal Article)