Immunogenic Heterogeneity of Renal Cell Carcinoma With Venous Tumor Thrombus.

OBJECTIVE: To perform immune-cell enumeration and programmed death-ligand 1 (PD-L1) expression in clear cell renal cell carcinoma (cc-RCC) with tumor thrombus (TT) to guide therapeutic decisions.

METHODS: After obtaining IRB approval and surgical consent, 6 patients underwent radical nephrectomy with venous tumor thrombectomy. We utilized RNA Sequencing to obtain RNAseq expression profiles. Computational calculation and enumeration of immune cells were performed using CIBERSORT, xCell, and ingenuity pathway analysis software. Statistical assessment was conducted using a t test, chi-square, ANOVA and Spearman rank correlations using SPSS v21.

RESULTS: We observed a higher proportion of M1 macrophages in the primary tumor and tumor thrombus, while we noted no difference in M2 macrophages despite M2 representing a high number in thrombus samples. (ANOVA, P = .032, and P = .89, respectively). Validation with xCell and ingenuity pathway analysis analysis showed a high involvement of macrophages. We observed a higher number of M1 macrophages (CIBERSORT mean 0.11 vs 0.03, P < 0.01) and (nonactivated) resting Natural Killer (NK) cells (0.077 vs 0.017, P = .02) associated PD-L1 high expression of the primary tumor. PDL1 expression was variable without differences in tumor stage, level, or immune cell detection. We observed an inverse correlation of mean platelet volume with PD-L1 expression within the primary tumor (Spearman, -0.89, P = 02) and the TT (Spearman, -0.77, P = 0.07).

CONCLUSION: Renal tumor thrombus has higher levels of M1 macrophages that could be utilized as additional targets for future drug development. The PD-L1 expression on clear cell RCC biopsy may not represent its corresponding TT. Future studies are needed to confirm mean platelet volume as a potential blood-based biomarker for PD-L1 expression in RCC.