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.

Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma

“…The results derived from the IHC analysis of our sample are quite similar to those previously reported in literature, particularly for ratio between CD4+ and CD8+ cells [ 18 ]; only a third of patients presented PD-L1 CPS above 1. Tumors without clear cell component were associated with higher ratio between CD80+ and CD163+ immune cells, reflecting distinct macrophage population between ccRCCs and nccRCCs [ 19 ].…”

MOICS, a novel classier deciphering immune heterogeneity and aid precise management of clear cell renal cell carcinoma at multiomics level

“…For instance, Rebuzzi et al demonstrated a strong correlation between the presence of specific immune cell types – particularly CD8 + T cells, CD4 + T cells, and PD-L1 expression – and patient responses to nivolumab treatment. 48 This correlation aligns with findings by Brown et al, who identified distinct expression patterns of immune markers differentiating responders from non-responders to ICIs. 49 These patterns are potentially predictive of treatment outcomes, suggesting that a nuanced understanding of tumor-infiltrating lymphocytes (TILs) could substantially refine the personalization of immunotherapy in RCC.…”