Abstract
Treatment options for metastatic renal cell carcinoma (RCC) have been expanding in the last years, from the consolidation of several anti-angiogenic agents to the approval of immune checkpoint inhibitors (ICIs). The rationale for the use of immunomodulating agents derived from the observation that RCC usually shows a diffuse immune-cell infiltrate. ICIs target Cytotoxic T Lymphocytes Antigen 4 (CTLA-4), programmed death 1 (PD-1), or its ligand (PD-L1), showing promising therapeutic efficacy in RCC. PD-L1 expression is associated with poor prognosis; however, its predictive role remains debated. In fact, ICIs may be a valid option even for PD-L1 negative patients. The establishment of valid predictors of treatment response to available therapeutic options is advocated to identify those patients who could benefit from these agents. Both local and systemic inflammation contribute to tumorigenesis and development of cancer. The interplay of tumor-immune status and of cancer-related systemic inflammation is pivotal for ICI-treatment outcome, but there is an unmet need for a more precise characterization. To date, little is known on the role of inflammation markers on PD-1 blockade in RCC. In this paper, we review the current knowledge on the interplay between inflammation markers, PD-1 axis, and anti-angiogenic agents in RCC, focusing on biological rationale, implications for treatment, and possible future perspectives.
Highlights
Renal cell carcinoma (RCC) is the seventh most common type of cancer in men and the tenth in women in Western countries [1,2]
We review the current knowledge on the interaction of inflammation and the PD-L1/PD-L1 axis in renal cell carcinoma (RCC), focusing on their possible role as prognostic and predictive factors in patients affected by these tumors and treated with immune-checkpoint inhibitors (ICIs) or anti-angiogenic agents
Shin et al demonstrated that PD-L1 expression is significantly related to poor response to VEGF-tyrosine kinase inhibitors (TKIs); in addition, PD-L1 is independently associated with shorter survival in metastatic
Summary
Renal cell carcinoma (RCC) is the seventh most common type of cancer in men and the tenth in women in Western countries [1,2]. RCC incidence has been increasing in the last 30 years, at an annual rate of around 3%, but the figures are recently showing a tendency of plateauing [3]. When all stages of RCC are considered, mortality rates seem to have leveled [4]. Two more categories of drugs became available, namely anti-angiogenic agents and mammalian target of rapamycin (mTOR) inhibitors. Immune-checkpoint inhibitors (ICIs) obtained indication at first as second-line treatment and are available as first-line treatment in metastatic RCC. We review the current knowledge on the interaction of inflammation and the PD-L1/PD-L1 axis in RCC, focusing on their possible role as prognostic and predictive factors in patients affected by these tumors and treated with ICIs or anti-angiogenic agents
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