High risk clear cell renal cell carcinoma microenvironments contain protumour immunophenotypes lacking specific immune checkpoints
Perioperative immune checkpoint inhibitor (ICI) trials for intermediate high-risk clear cell renal cell carcinoma (ccRCC) have failed to consistently demonstrate improved patient outcomes. These unsuccessful ICI trials suggest that the tumour infiltrating immunophenotypes, termed here as the immune cell types, states and their spatial location within the tumour microenvironment (TME), were unfavourable for ICI treatment. Defining the tumour infiltrating immune cells may assist with the identification of predictive immunophenotypes within the TME that are favourable for ICI treatment. To define the immunophenotypes within the ccRCC TME, fresh para-tumour (pTME, n = 2), low-grade (LG, n = 4, G1-G2) and high-grade (HG, n = 4, G3-G4) tissue samples from six patients with ccRCC presenting at a tertiary referral hospital underwent spatial transcriptomics sequencing (ST-seq). Within the generated ST-seq datasets, immune cell types and states, termed here as exhausted/pro-tumour state or non-exhausted/anti-tumour state, were identified using multiple publicly available single-cell RNA and T-cell receptor sequencing datasets as references. HG TMEs revealed abundant exhausted/pro-tumour immune cells with no consistent increase in expression of PD-1, PD-L1 and CTLA4 checkpoints and angiogenic genes. Additional HG TME immunophenotype characteristics included: pro-tumour tissue-resident monocytes with consistently increased expression of HAVCR2 and LAG3 checkpoints; an exhausted CD8+ T cells sub-population with stem-like progenitor gene expression; and pro-tumour tumour-associated macrophages and monocytes within the recurrent TME with the expression of TREM2. Whilst limited by a modest sample size, this study represents the largest ST-seq dataset on human ccRCC. Our study reveals that high-risk ccRCC TMEs are infiltrated by exhausted/pro-tumour immunophenotypes lacking specific checkpoint gene expression confirming that HG ccRCC TME are immunogenic but not ICI favourable.
详见LabEx网站(
www.u-labex.com)或来电咨询!
基因水平:PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平:MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平:细胞染色、细胞分选、细胞培养、细胞功能
组织水平:空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析:流式数据分析、组化数据分析、多因子数据分析
基因水平:PCR Array、RT-PCR、PCR、单细胞测序
蛋白水平:MSD、Luminex、CBA、Elispot、Antibody Array、ELISA、Sengenics
细胞水平:细胞染色、细胞分选、细胞培养、细胞功能
组织水平:空间多组学、多重荧光免疫组化、免疫组化、免疫荧光
数据分析:流式数据分析、组化数据分析、多因子数据分析
联系电话:4001619919
联系邮箱:labex-mkt@u-labex.com
公众平台:蛋白检测服务专家
联系邮箱:labex-mkt@u-labex.com
公众平台:蛋白检测服务专家

本网站销售的所有产品及服务均不得用于人类或动物之临床诊断或治疗,仅可用于工业或者科研等非医疗目的。