Increased angiogenesis and tumor induced immune evasion are two mechanisms by which clear cell renal cell carcinoma (ccRCC) proliferate and metastasize; however the relationship between these pathways in human ccRCC tumor samples is poorly understood. We conducted a nested case control study by identifying PDL1 positive by immunohistochemistry (IHC) primary ccRCC tumors that we matched on the Mayo SSIGN score with PDL1 negative primary ccRCC tumors. From these tumors we extracted RNA from FFPE slides and quantified gene expression of VEGFA, VEGFR1, VEGFR2, and PDL1. In addition, we also assessed tumor-infiltrating lymphocytes by IHC for CD3. We then analyzed the relationship between VEGFA, VEGFR1, VEGFR2, CD3, and PDL1. When analyzed as a continuous variable, PDL1 protein expression by IHC inversely correlates with the expression of the three VEGF related genes: VEGFA (r=-0.23, p=0.01), VEGFR1 (r=-0.34, p<0.001), and VEGFR2 (r=-0.23, p=0.01). When dichotomized, the PDL1 positive cohort trended towards a lower expression of VEGFA (fold change=0.72, p=0.056) and VEGFR1 (fold change=0.69, p=0.057). In addition, there was a significant and positive relationship between TIL as assessed by IHC for CD3 and PDL1 by IHC (r=0.25, p=0.015), and there was a trend towards an inverse relationship between TIL and VEGFA gene expression (r=-0.18, p=0.089). In conclusion, we are the first demonstrate an inverse association between the angiogenesis and PDL1 in primary ccRCC human tumor samples, and that this relationship may be related to the immune suppressive effects of VEGF signaling.
- Received April 15, 2013.
- Revision received July 26, 2013.
- Accepted August 16, 2013.
- Copyright © 2013, American Association for Cancer Research.