Abstract 156P
Background
Toll-like receptor 3 (TLR3) is an innate immune pattern recognition receptor that can be activated by viral dsRNA and damage-associated molecular patterns, such as self-derived RNA from tissue necrosis. TLR3 signaling has a unique role in in promoting tumor-infiltrating cytotoxic T lymphocyte (CTL), it is associated with improved clinical outcome in patients (pts) with clear cell renal cell carcinoma (ccRCC). In this study, we assess the prognostic value of TLR3.
Methods
Genomic and clinically data were obtained from The Cancer Genome Atlas PanCancer Atlas databases. Pts with RNA-seq data at all stages were included. The mean TLR-3 mRNA expressions in transcript per million were compared by Wilcoxon tests. ccRCC pts were divided into TLR-3 high and low groups, at the 50th percentile. The progression free survival (PFS) and overall survival (OS) differences were compared between the two groups and the significance was determined by Log-rank test. The OS was modeled as a function of TLR3 expression, cancer stage, and tumor grade using Cox regression in a multivariate analysis.
Results
510 ccRCC pts were included and 83 (16.3%) had stage IV diseases. ccRCC had highest TLR3 mRNA expression among the 19 solid tumor types studied in TCGA (p<0.001). The mean TLR3 expression of primary ccRCC was 5.5-fold higher than the next highest expresser (papillary RCC, n=290) and 9.9-fold higher than the mean of the 17 others. Among the 72 pts with matched benign kidney tissue, 67 (93%) had increased TLR3 expression in the cancer. On average, there was 225% increase of intratumoral TLR3 expression compared to the benign counterpart tissue (p<0.001). The median OS was not reached (NR) in TLR3 high (95% CI: 93m-NR) vs. 62m in TLR3 low (95% CI: 52.2-79.5m). The hazard ratio (HR) was 0.41 (p<0.001). High TLR3 was associated with improved PFS (HR=0.44, 95% CI: 0.31-0.61). In multivariate analysis, high TLR3 predicts better OS independent of stage and grade (HR=0.40, CI 95% 0.23-0.57, p<0.001).
Conclusions
High intratumoral TLR3 expression at the time of nephrectomy may be an independent predictor of improved survival in pts with ccRCC. Future studies are needed to further delineate the relationships between TLR3 expression, CTL recruitment, and anticancer immune response.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.