• renal cell carcinoma
• immunotherapy
• tumor microenvironment

Immunotherapy-based combination treatment dramatically changed therapeutic landscape in previous untreated advanced RCC. However, despite a clear survival benefit, metastatic RCC remains incurable: most patients develop disease progression, requiring the choice of a new systemic treatment, and up to 20% of patients are refractory to combination treatments, rapidly developing disease progression.
Several biomarkers that can predict response to ICI in first-line of RCC are under investigation, but none are approved for use in clinical practice. Recently, more attention has been given to the role of the TME in modulating the response to systemic therapies. In particular, due to the high density of immune cells (such as T cells and tumor-associated macrophages, TAMs), the evaluation of TME in RCC samples could represent a simple and useful assessment to identify potential biomarkers of response to ICIs. Detection by IHC of cluster of differentiation (CD) related to immune checkpoints and immune cells represents a well-established, readily available and economic method to study TME.
The purpose of our study is to provide pathological characterization through immunohistochemical evaluation of TME in RCC tumor samples from patients who had received immune-based combination therapy as first-line treatment for advanced disease and to find preliminary evidence about their possible correlation with clinical efficacy and activity of these treatments.
Despite various limitations (mainly retrospective nature and small sample size), our findings confirm the important role of TME, and, in particular, of some cell populations (such as CD163+ macrophages) in identifying a subset of patients with worse clinical outcome after receiving immune checkpoint blockers as first-line treatment.