Microbiome within Primary Tumor Tissue from Renal Cell Carcinoma May Be Associated with PD-L1 Expression of the Venous Tumor Thrombus

Objective: To perform a proof of concept microbiome evaluation and PD-L1 expression profiling in clear-cell renal cell carcinoma (cc-RCC) with associated tumor thrombus (TT).

Methods: After IRB approval, six patients underwent radical nephrectomy (RN) with venous tumor thrombectomy (VTT). We collected fresh tissue specimens from normal adjacent, tumor, and thrombus tissues. We utilized RNA sequencing to obtain PD-L1 expression profiles and perform microbiome analysis. Statistical assessment was performed using Student's t-test, chi-square, and spearman rank correlations using SPSS v25.

Results: We noted the tumor thrombus to be mostly devoid of diverse microbiota. A large proportion of Staphylococcus epidermidus was detected and unknown if this is a surgical or postsurgical contaminant; however, it was noted more in the thrombus than other tissues. Microbiome diversity profiles were most abundant in the primary tumor compared to the thrombus or normal adjacent tissue. Differential expression of PD-L1 was examined in the tumor thrombus to the normal background tissue and noted three of the six subjects had a threshold above 2-fold. These three similar subjects had foreign microbiota that are typical residents of the oral microbiome.

Conclusion: Renal tumors have more diverse microbiomes than normal adjacent tissue. Identification of resident oral microbiome profiles in clear-cell renal cancer with tumor thrombus provides a potential biomarker for thrombus response to PD-L1 inhibition.