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

Abstract

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.

Characteristics of Gut Microbiota in Patients With Clear Cell Renal Cell Carcinoma

“…Streptococcus was also more abundant in prostate cancer, while PICRUSt data indicated that B vitamin metabolic pathways, which are protective against prostate cancer risk, were down-regulated in prostate cancer patients ( Liss et al, 2018 ). Surprisingly, Streptococcus was more abundant in ccRCC tissue than in normal kidney tissue, which suggested an association with tumorigenesis ( Liss et al, 2020 ). In our study, using Tax4Fun functional predictions, ABC transporter genes were more active in ccRCC.…”

The Interaction Between the Microbiome and Tumors

“…Metabolites of the microbiome also affect treatment outcomes ( Hatae et al., 2020 ; Nomura et al., 2020 ). Therefore, the microbiome can serve as a potential biomarker or target to distinguish the precision therapeutic strategies for different cancer patients ( Hargadon, 2017 ; Shaikh et al., 2019 ; Liss et al., 2020 ; Liu et al., 2020 ; Song et al., 2020 ). Meanwhile, the human commensal bacteria, such as Lactobacilli and Bifidobacteria have also been suggested to play important roles in preventing and treating various tumor malignancies, indicating that the microbiome can be a source of potential therapeutics, as well as a therapeutic target ( Motevaseli et al., 2017 ; Wei et al., 2018 ; Legesse Bedada et al., 2020 ; Zuo et al., 2020 ).…”

Precision Medicine: An Optimal Approach to Patient Care in Renal Cell Carcinoma

“…Hence, harnessing the positive effect of gut microbiota in patients with RCC can enhance the clinical efficacy of ICI therapy ( 198 ). Few other studies have also emphasized the importance of modulating gut microflora to achieve successful outcomes while using ICIs on patients with mRCC ( 199 , 200 ).…”