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Positive intratumoral chemokine (C-C motif) receptor 8 expression predicts high recurrence risk of post-operation clear-cell renal cell carcinoma patients.

ABSTRACT: Chemokine (C-C motif) receptor 8 (CCR8) could drive cancer progress through recruiting certain immune cells. Recent evidences revealed the chemotaxis of CCR8+ human malignant tumor cells towards lymph node, and a significantly increased CCR8 expression in renal carcinomas patients. To assess the clinical association between CCR8 expression and the risk of post-surgery recurrence in patients with clear-cell renal cell carcinoma (ccRCC), we detected intratumoral CCR8 expression in 472 post-nephrectomy ccRCC patients retrospectively enrolled. Positive CCR8 staining tumor cell occurred in 26.1% (123 of 472) non-metastatic ccRCC cases, and the positive expression was associated with increased risks of recurrence (Log-Rank P < 0.001). In multivariate analyses, CCR8 expression was identified as an independent prognostic factor (P = 0.008) and entered into a newly-built nomogram together with T stage, Fuhrman grade, tumor size, necrosis and lymphovascular invasion. Calibration curves showed optimal agreement between predictions and observations, while its C-index was higher than that of Leibovich score for predicting recurrence-free survival (RFS) of localised RCC patients (0.854 vs 0.836, respectively; P = 0.044). The practical prognostic nomogram model may help clinicians in decision making and design of clinical studies.

SUBMITTER: Fu Q

PROVIDER: S-EPMC4885002 | biostudies-literature | 2016 Feb

REPOSITORIES: biostudies-literature

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Positive intratumoral chemokine (C-C motif) receptor 8 expression predicts high recurrence risk of post-operation clear-cell renal cell carcinoma patients.

Fu Qiang Q Chang Yuan Y Zhou Lin L An Huimin H Zhu Yu Y Xu Le L Zhang Weijuan W Xu Jiejie J

Oncotarget 20160201 7

Chemokine (C-C motif) receptor 8 (CCR8) could drive cancer progress through recruiting certain immune cells. Recent evidences revealed the chemotaxis of CCR8+ human malignant tumor cells towards lymph node, and a significantly increased CCR8 expression in renal carcinomas patients. To assess the clinical association between CCR8 expression and the risk of post-surgery recurrence in patients with clear-cell renal cell carcinoma (ccRCC), we detected intratumoral CCR8 expression in 472 post-nephrec ...[more]

PMID: 26716905

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Project description:Background and aimsHepatocellular carcinoma (HCC) is an aggressive malignancy which is often associated with a complex tumor microenvironment attributable to etiology-induced cellular inflammation. γδ T cells are known to detect and react to chronic inflammation, which is linked to cancer development, progression, and metastasis. Our recent genomic study revealed an increased infiltration of several immune cell types, including γδ T cells, in tumor microenvironments of a Thai HCC subtype associated with a good prognosis.Approach and resultsHere, we quantified the amount of γδ T cells using a γδ T-cell-specific gene signature in 247 Chinese HCC patients. We also validated the γδ T-cell signature in American HCC patients. Additionally, such an association was only found in tumor transcriptomic data, but not in adjacent nontumor transcriptomic data, suggesting a selective enrichment of γδ T cells in the tumor microenvironment. Moreover, the γδ T-cell signature was positively correlated with the expression of natural killer cell receptor genes, such as NKG2D and cytolytic T-cell genes granzymes and perforin, suggesting a stronger T-cell-mediated cytotoxic activity. Furthermore, we found that the γδ T-cell-specific gene expression is positively correlated with the expression of chemokine (C-C motif) ligand 4 (CCL4)/chemokine (C-C motif) ligand 5 (CCL5) and C-C chemokine receptor type 1 (CCR1)/C-C chemokine receptor type 5 (CCR5), the receptors for γδ T cells. We validated these results using immunohistochemical analysis of formalin-fixed, paraffin-embedded tumor biopsies from 182 HCC patients. Moreover, we found evidence of CCL4/CCL5-mediated recruitment of γδ T cells both in vitro and in a murine orthotopic Hepa1-6 HCC model.ConclusionsWe propose that CCL4/CCL5 may interact with their receptor, CCR1/CCR5, which may facilitate the recruitment of γδ T cells from peripheral blood or peritumor regions to the tumor regions. Consequently, an increasing infiltration of γδ T cells in tumors may enhance antitumor immunity and improve patients' prognosis.

Dataset Information

Positive intratumoral chemokine (C-C motif) receptor 8 expression predicts high recurrence risk of post-operation clear-cell renal cell carcinoma patients.

Publications

Positive intratumoral chemokine (C-C motif) receptor 8 expression predicts high recurrence risk of post-operation clear-cell renal cell carcinoma patients.

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