Sarcopenic Obesity and its Prognostic Impact on Urological Cancers: A Systematic Review.

PURPOSE: Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and significance of sarcopenic obesity are not well understood. We systematically reviewed data on the prevalence and prognostic impact of sarcopenic obesity for patients with renal cell carcinoma, urothelial carcinoma and prostate cancer undergoing treatment. MATERIALS AND METHODS: We searched EMBASE®, PubMed®/MEDLINE® and Scopus® for relevant original articles and abstracts published between January 2010 and February 2021. Primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival. The secondary outcome was the prevalence of sarcopenic obesity. RESULTS: A total of 15 studies comprising 3,866 patients were included. Of the 10 studies that evaluated survival outcomes, the association between sarcopenic obesity and survival was mixed. One of 10 studies showed a significant association of sarcopenic obesity with OS (HR 0.7, 95% CI 0.51-0.98; p=0.04). One additional study showed reported a trend for shorter OS (p=0.05) associated with sarcopenic obesity. Others reported that it is an adverse prognostic factor for CSS (HR 5.0, 95% CI 1.4-16.7; p=0.01). All other studies did not demonstrate that sarcopenic obesity was of prognostic relevance with regard to OS, CSS and progression-free survival. Overall, its mean prevalence was 27% (range 11-63). CONCLUSIONS: There is considerable heterogeneity in methods used to define sarcopenic obesity in the literature, and current data are limited. Future studies are needed to further understand the relationship of obesity and sarcopenia on the clinical trajectory of patients with urological cancer.

Platelet PD-L1 suppresses anti-cancer immune cell activity in PD-L1 negative tumors.

Strategies that interfere with the binding of the receptor programmed cell death protein-1 (PD-1) to programmed death ligand-1 (PD-L1) have shown marked efficacy against many advanced cancers, including those that are negative for PD-L1. Precisely why patients with PD-L1 negative tumors respond to PD-1/PD-L1 checkpoint inhibition remains unclear. Here, we show that platelet-derived PD-L1 regulates the growth of PD-L1 negative tumors and that interference with platelet binding to PD-L1 negative cancer cells promotes T cell-induced cancer cytotoxicity. These results suggest that the successful outcomes of PD-L1 based therapies in patients with PD-L1 negative tumors may be explained, in part, by the presence of intra-tumoral platelets. Altogether, our findings demonstrate the impact of non-cancer/non-immune cell sources of PD-L1 in the tumor microenvironment in the promotion of cancer cell immune evasion. Our study also provides a compelling rationale for future testing of PD-L1 checkpoint inhibitor therapies in combination with antiplatelet agents, in patients with PD-L1 negative tumors.