Absent Toll-like receptor-9 expression predicts poor prognosis in renal cell carcinoma

Abstract

BackgroundToll-like receptor 9 (TLR9) is a cellular DNA-receptor whose activation with cognate ligands triggers an immune reaction, with increased production of inflammatory cytokines. The aim of this study was to examine the expression of TLR9 in renal cell carcinoma (RCC), which is generally renowned of its immunogenic nature. We also evaluated the prognostic value of TLR9 in RCC.MethodsTLR9 expression in RCC was characterized with immunohistochemistry in a retrospective study population of 152 RCC patients who underwent renal surgery. The TLR9 staining intensity was compared with clinical parameters.ResultsOf the studied tumours, 112 (81%) exhibited cytoplasmic TLR9 immunostaining. No association was detected between cytoplasmic TLR9 immunoexpression intensity and stage, nuclear grade, histological subtype or tumour necrosis. Cytoplasmic TLR9 immunoexpression was, however, a marker of favourable RCC specific survival both in univariate analysis and in multivariate regression model.ConclusionsWe conclude that TLR9 expression is an independent prognostic marker of RCC and the absence of TLR9 expression is related to poorer prognosis in RCC.

Biopathological Significance of TLR9 Expression in Cancer Cells and Tumor Microenvironment Across Invasive Breast Carcinomas Subtypes

“…TLR9 overexpression by cancer epithelial [35][36][37][38][39][40][41]. Results from our study are in agreement with those reported in the literature [42].…”

SPLUNC1 reduces the inflammatory response of nasopharyngeal carcinoma cells infected with the EB virus by inhibiting the TLR9/NF-κB pathway

“…The interaction of these motifs with the TLRs triggers a cascade of signaling events which stimulate the products of pro-inflammatory cytokines and chemokines to respond to the invading pathogen. As a member of the TLR family, TLR9 expression is noted in many malignancies, such as lung and cervical cancer and NPC (30)(31)(32)(33). TLR9 activation can induce high expression of cytokines and chemokines, cause tumorinflammatory microenvironment formation and promote the occurrence and development of malignancies (34,35).…”

Tumor infiltrating CD8+T lymphocyte count is independent of tumor TLR9 status in treatment naïve triple negative breast cancer and renal cell carcinoma

“…11 Of the RCC specimens previously analyzed for TLR9 expression (n D 152), 94 were evaluable in this study for tumor infiltrating CD8 C T lymphocytes. The reasons for the lack of complete cohort included loss of the tumor blocks or folding of the specimens during antigen retrieval and/or staining.…”

“…4,6 Although initially thought to be limited only to the innate immune system, it is now well established that TLR9 is widely expressed also in various cancer types, such as in breast, brain, gastric, lung, ovarian, prostate and kidney cancers as well as in cancers of the GI tract. [7][8][9][10][11][12][13][14][15][16][17] Stimulation of TLR9 expressing cancer cells with bacterial DNA-like, synthetic TLR9 ligands induces MMP-13-mediated invasion in vitro. 7,10,18,19 Based on these findings, it was expected that tumor TLR9 mediates invasion and metastasis and that high tumor TLR9 expression would be associated with worse survival.…”

“…In these cancers, low tumor TLR9 expression has been shown to predict poor prognosis and short disease-specific survival. 11,13 Among breast cancer patients, those with TNBC are considered to have the worst prognosis. 21,22 This is because of the generally aggressive behavior of such tumors and also because these tumors lack the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2), which would allow targeted treatment.…”