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+ T lymphocytes with TLR9 expression in treatment naïve
breast cancer (n = 197) and RCC (n = 94) cohorts with known TLR9 expression status. CD8+ T lymphocyte counts were assayed with image analysis after immunohistochemistry (IHC).
Tumor TLR9 expression was not correlated with CD8+ T cell counts in
breast cancer or RCC. CD8+ T cell counts were significantly associated with
tumor proliferation index in TNBC, but not in non-TNBC. CD8+ T cell counts were also significantly associated with
tumor grade in non-TNBC, but not in TNBC. In RCC, CD8+ T cell counts were significantly associated with
tumor stage. CD8+ T cell counts were significantly associated with prognosis in TNBC and RCC, but the presence of CD8+ T cells in these
tumors had opposite effects on disease-specific survival: High CD8+ counts were associated with better prognosis in TNBC and worse prognosis in RCC. Among TNBC patients, those with low
tumor TLR9 and low CD8+ T cell counts had the poorest prognosis (log-rank p = 0.0002 vs. high
tumor TLR9 and high CD8+ T cell count). In conclusion, pre-treatment
tumor TLR9 status is not associated with
tumor infiltrating CD8+ T lymphocytes in TNBC or RCC. The combination of TLR9 and CD8+ TIL count might be a novel composite prognostic marker in TNBC.