Analyses of tumor microenvironment in patients with advanced renal cell carcinoma receiving immunotherapy (Meet-URO 18 study)

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months).
Areas covered: The current study includes extensive immunohistochemical analysis of T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression on tumor cells, and PD-L1 expression, on an increased sample size including 161 tumor samples (113 patients) compared with preliminary presented data. Responders‘ tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression (p = 0.014), higher CD56 expression (p = 0.046) and higher CD8/CD4 ratio (p = 0.030).
Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy.
There is a critical lack of predictive biomarkers for patients with metastatic renal cell carcinoma receiving immunotherapy, therefore the identification of patients likely to benefit from this treatment represents a pressing clinical challenge.
The Meet-URO 18 study is a multicentric, retrospective, translational study that delves into the immune tumor microenvironment (I-TME) of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line or beyond. Patients were categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months).
Digital multitarget immunohistochemical analyses were performed on the I-TME of tumor samples of primary tumors or metastases.
Primary analyses revealed that responders exhibited lower CD4 expression and higher levels of phosphorylated mTOR and CD56.
Further extensive analysis of the I-TME focused on T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression assessed on tumor cells, and PD-L1 expression (SP263) assessed on both tumor and immune cells.
Responders tumor tissue showed significantly lower CD4 expression, higher CD56 expression and a higher CD8/CD4 ratio compared with non-responders.
Other parameters, including PD-L1 expression, did not reach statistical significance.
This secondary analysis highlights the emerging significance of CD56 as a putative biomarker for immunotherapy, suggesting a critical role for regulatory CD4+ cells over cytotoxic CD8+ cells.