Abstract
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.
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Article info
Publication history
Published online: October 29, 2018
Footnotes
Financial disclosure: The authors declare that they have no relevant financial interests.
Identification
Copyright
© 2018 Elsevier Inc. All rights reserved.
