Toll-like receptor 9 (TLR9) is a cellular DNA-receptor of the innate immune system that is widely expressed in cancers. We demonstrated that low tumor TLR9 expression predicts poor disease-specific survival in triple negative breast cancer (TNBC) and renal cell carcinoma (RCC). We hypothesized that this is because TLR9 expression affects tumor immunophenotype. To begin to test this, we compared the number of tumor infiltrating CD8 C T lymphocytes with TLR9 expression in treatment na€ ıve breast cancer (n D 197) and RCC (n D 94) cohorts with known TLR9 expression status. CD8 C T lymphocyte counts were assayed with image analysis after immunohistochemistry (IHC). Tumor TLR9 expression was not correlated with CD8C T cell counts in breast cancer or RCC. CD8 C T cell counts were significantly associated with tumor proliferation index in TNBC, but not in non-TNBC. CD8C T cell counts were also significantly associated with tumor grade in non-TNBC, but not in TNBC. In RCC, CD8C T cell counts were significantly associated with tumor stage. CD8 C T cell counts were significantly associated with prognosis in TNBC and RCC, but the presence of CD8 C T cells in these tumors had opposite effects on disease-specific survival: High CD8 C counts were associated with better prognosis in TNBC and worse prognosis in RCC. Among TNBC patients, those with low tumor TLR9 and low CD8 C T cell counts had the poorest prognosis (log-rank p D 0.0002 vs. high tumor TLR9 and high CD8 C T cell count). In conclusion, pre-treatment tumor TLR9 status is not associated with tumor infiltrating CD8 C T lymphocytes in TNBC or RCC. The combination of TLR9 and CD8 C TIL count might be a novel composite prognostic marker in TNBC.
CD73 is a 5' ectonuclease that catalyzes the conversion of cyclic AMP into the highly immunosuppressive adenosine in extracellular space. In addition to the cells of the immune system, CD73 is highly expressed in various cancer cell lines and clinical cancer tissues. Toll like receptor-9 (TLR9) is a cellular DNA-receptor that is highly expressed in breast cancer. Both CD73 and TLR9 expression have recently been associated with TNBC prognosis but the mechanisms how these proteins possibly contribute to TNBC pathophysiology remains poorly understood. TLR9 and CD73 expression has been shown to be mutually regulated in various cell types. Whether this is the case in cancer is unknown. The aim of this study was to investigate the mutual role of TLR9 and CD73 in breast cancer (BC). Specifically our hypothesis was that TLR9 and CD73 expression correlate in TNBC. We compared immunohistological tumor TLR9 and CD73 expression scores using a previously characterized breast cancer (BC) cohort (n=184) with follow-up time of > 10 years. We did not discover a connection between TLR9 and CD73 expression in tumor cells in BC. There was a trend for increased survival among patients that had high tumor cell CD73 expression, as compared with the lower tumor cell CD73 expression groups. There was a trend for a better survival among TNBC patients that had lower stromal CD73 expression, as compared with those TNBC patients that had higher stromal CD73 expression. No such difference was detected among patients with non-TNBC tumors. Our results suggest that stromal vs. tumor cell CD73 expression have opposite effects on survival in TNBC, but there is no connection between CD73 and TLR9 expression. Our conclusions are limited by low sample numbers. Citation Format: Selander K, Mella M, Kauppila J, Karihtala P, Jukkola-Vuorinen A, Auvinen P, Soini Y, Kauppila S, Haapasaari K-M, Harris K, Vuopala K. Comparison of tumor and stroma CD73 expression with TLR9 and survival in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-04-13.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.