Immune Cells and Antibody Engineering Research Center of Guizhou Province/Key Laboratory of Biology and Medical Engineering, Guizhou Medical University, Guiyang, China.
School of Biology and Engineering, Guizhou Medical University, Guiyang, China.
Cancer Sci. 2019 May;110(5):1564-1572. doi: 10.1111/cas.13996. Epub 2019 Apr 7.
Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma (RCC). Tumor-infiltrating immune cells (TIICs) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIICs in RCC and further reveal the independent prognostic values of TIICs. CIBERSORT, an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIICs and immune checkpoint modulators with overall survival (OS). We found that CD8+ T cells were associated with prolonged OS (hazard ratio [HR] = 0.09, 95% confidence interval [CI].01-.53; P = 0.03) in chromophobe carcinoma (KICH). A higher proportion of regulatory T cells was associated with a worse outcome (HR = 1.59, 95% CI 1.23-.06; P < 0.01) in renal clear cell carcinoma (KIRC). In renal papillary cell carcinoma (KIRP), M1 macrophages were associated with a favorable outcome (HR = .43, 95% CI .25-.72; P < 0.01), while M2 macrophages indicated a worse outcome (HR = 2.55, 95% CI 1.45-4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA4 and LAG3 were associated with a poor prognosis in KIRC, and IDO1 and PD-L2 were associated with a poor prognosis in KIRP. This study indicates TIICs are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development.
肿瘤的免疫浸润与肾细胞癌（RCC）的临床结局密切相关。肿瘤浸润免疫细胞（TIICs）调节癌症的进展，是有吸引力的治疗靶点。本研究旨在确定 RCC 中 TIIC 的组成，并进一步揭示 TIIC 的独立预后价值。CIBERSORT 是一种已建立的算法，用于根据 891 个肿瘤的基因表达谱估计 22 种免疫细胞类型的比例。Cox 回归用于评估 TIIC 和免疫检查点调节剂与总生存期（OS）的相关性。我们发现，在嫌色细胞癌（KICH）中，CD8+T 细胞与延长 OS 相关（风险比 [HR] = 0.09，95%置信区间 [CI] 0.01-0.53；P = 0.03）。调节性 T 细胞比例较高与肾透明细胞癌（KIRC）预后较差相关（HR = 1.59，95%CI 1.23-0.06；P < 0.01）。在肾乳头状细胞癌（KIRP）中，M1 巨噬细胞与良好的结局相关（HR = 0.43，95%CI 0.25-0.72；P < 0.01），而 M2 巨噬细胞则表明预后较差（HR = 2.55，95%CI 1.45-4.47；P < 0.01）。此外，免疫调节剂分子 CTLA4 和 LAG3 与 KIRC 的预后不良相关，IDO1 和 PD-L2 与 KIRP 的预后不良相关。本研究表明 TIICs 是 RCC 预后的重要决定因素，同时揭示了免疫治疗开发的潜在靶点和生物标志物。
