■表观遗传机制在激活中起着至关重要的作用,分化,和免疫细胞的效应子功能。乳腺和肾脏表达的趋化因子(CXCL14)主要有助于调节免疫细胞。然而,其在塑造肿瘤免疫微环境(TIME)中的作用在肾细胞癌(RCC)中尚未阐明。
■本研究旨在阐明CXCL14在预测RCC患者免疫治疗疗效中的作用。
■CXCL14表达和RNA测序,单细胞RNA测序(scRNA-seq),并分析了来自公共数据库的RCC生存数据集,比较不同CXCL14水平之间的生存率。用TIMER2.0和基因表达谱交互分析分析CXCL14与免疫浸润和人类白细胞抗原(HLA)基因表达的相关性。使用机构scRNA-seq和免疫组织化学染色分析来验证CXCL14表达水平与免疫疗法功效之间的关系。
■CXCL14在RCC的成纤维细胞和恶性细胞中表达,和更高的表达与更好的生存相关。富集分析显示CXCL14参与免疫激活,主要是在抗原游行中,抗原呈递,和主要的组织相容性复合体组装。CXCL14表达与T细胞浸润和HLA相关基因表达呈正相关。在Checkmate025中接受nivolumab的RCC队列中,CXCL14高表达的患者在免疫治疗后的总生存率优于CXCL14低表达的患者。scRNA-seq揭示了免疫治疗应答者中的一组CXCL14+成纤维细胞。免疫组织化学分析证实CXCL14高表达的患者同时CD8高表达的比例增加。RCC中CXCL14的表达水平与CXCR4的表达有关。
■CXCL14表达与RCC的免疫治疗反应相关。它是用于免疫疗法反应预测的有前途的生物标志物,并且可能是与免疫疗法方法组合的有效表观遗传调节剂。
CXCL14作为肾癌免疫治疗反应的潜在预测因子肾表达趋化因子(CXCL14)调节免疫细胞.我们根据公共和私人数据库和染色研究了它如何影响人体对肾癌的免疫反应。我们发现,肾癌中更高的CXCL14水平与更好的患者生存率有关。CXCL14似乎有助于激活免疫系统。当CXCL14水平高的患者接受免疫治疗时,它们往往比低水平的存活时间更长。具有CXCL14的成纤维细胞存在于对免疫疗法有反应的患者中。进一步的测试证实,高CXCL14水平与更多的免疫细胞有关。CXCR4可能是其在肾癌中的受体。这表明测量CXCL14水平可以帮助预测患者对肾癌免疫疗法的反应程度。
UNASSIGNED: Epigenetic mechanisms play vital roles in the activation, differentiation, and effector function of immune cells. The breast and kidney-expressed chemokine (CXCL14) mainly contributes to the regulation of immune cells. However, its role in shaping the tumor immune microenvironment (TIME) is yet to be elucidated in renal cell carcinoma (RCC).
UNASSIGNED: This study aimed to elucidate the role of CXCL14 in predicting the efficacy of immunotherapy in patients with RCC.
UNASSIGNED: CXCL14 expression and RNA-sequencing, single-cell RNA-sequencing (scRNA-seq), and survival datasets of RCC from public databases were analyzed, and survival was compared between different CXCL14 levels. The correlation between CXCL14 and immune infiltration and human leukocyte antigen (HLA) gene expression was analyzed with TIMER2.0 and gene expression profiling interactive analysis. Institutional scRNA-seq and immunohistochemical staining analyses were used to verify the relationship between CXCL14 expression level and the efficacy of immunotherapy.
UNASSIGNED: CXCL14 was expressed in fibroblast and malignant cells in RCC, and higher expression was associated with better survival. Enrichment analysis revealed that CXCL14 is involved in immune activation, primarily in antigen procession, antigen presentation, and major histocompatibility complex assemble. CXCL14 expression was positively correlated with T-cell infiltration as well as HLA-related gene expression. Among the RCC cohort receiving nivolumab in Checkmate 025, the patients with CXCL14 high expression had better overall survival than those with CXCL14 low expression after immunotherapy. scRNA-seq revealed a cluster of CXCL14+ fibroblast in immunotherapy responders. Immunohistochemistry analysis verified that the patients with high CXCL14 expression had an increased proportion of high CD8 expression simultaneously. The expression level of CXCL14 was associated with CXCR4 expression in RCC.
UNASSIGNED: CXCL14 expression is associated with immunotherapy response in RCC. It is a promising biomarker for immunotherapy response prediction and may be an effective epigenetic modulator in combination with immunotherapy approaches.
CXCL14 as potential predictor for immunotherapy response in kidney cancer Kidney-expressed chemokine (CXCL14) regulates immune cells. We studied how it affects the body’s immune response to kidney cancer based on public and private database and staining. We found that higher levels of CXCL14 in kidney cancer were linked to better patient survival. CXCL14 seems to help activate the immune system. When patients with high CXCL14 levels received immunotherapy, they tended to survive longer than those with low levels. Fibroblasts with CXCL14 were present in patients responding to immunotherapy. Further tests confirmed that high CXCL14 levels were related to more immune cells. CXCR4 may be its receptor in kidney cancer. This suggests that measuring CXCL14 levels could help predict how well a patient might respond to immunotherapy for kidney cancer.