小柯机器人

美国德克萨斯大学王凌华团队发现胃腺癌(GAC)进展过程中免疫和基质细胞状态和生态型的演变。相关论文发表在2023年7月6日出版的《癌细胞》杂志上。

他们对癌前病变、局部和转移性GAC进行了单细胞分析，确定了随着GAC的进展，肿瘤微环境(TME)细胞状态和组成的变化。大量IgA+浆细胞存在于癌前微环境中，而免疫抑制的髓细胞亚群和基质亚群在晚期GACs中占主导地位。

他们鉴定出6种TME生态型(EC1-6)。EC1只存在于血液中，而EC4、EC5和EC2分别在未累及组织、癌前病变和转移灶中高度富集。EC3和EC6是原发性GAC的两种不同生态型，与组织病理学和基因组特征以及生存结果相关。广泛的间质重塑发生在GAC进展中。SDC2在癌症相关成纤维细胞(CAFs)中的高表达与侵袭性表型和低存活率有关，而SDC2在CAFs中的过表达有助于肿瘤生长。

他们的研究提供了一个高分辨率的GAC TME图谱，并强调了进一步研究的潜在目标。

据了解，了解GAC进展过程中的TME重编程可能会发现新的治疗靶点。

附：英文原文

Title: Evolution of immune and stromal cell states and ecotypes during gastric adenocarcinoma progression

Author: Ruiping Wang, Shumei Song, Jiangjiang Qin, Katsuhiro Yoshimura, Fuduan Peng, Yanshuo Chu, Yuan Li, Yibo Fan, Jiankang Jin, Minghao Dang, Enyu Dai, Guangsheng Pei, Guangchun Han, Dapeng Hao, Yating Li, Deyali Chatterjee, Kazuto Harada, Melissa Pool Pizzi, Ailing W. Scott, Ghia Tatlonghari, Xinmiao Yan, Zhiyuan Xu, Can Hu, Shaowei Mo, Namita Shanbhag, Yang Lu, Matheus Sewastjanow-Silva, Ahmed Adel Fouad Abdelhakeem, Guang Peng, Samir M. Hanash, George A. Calin, Cassian Yee, Pawel Mazur, Autumn N. Marsden, Andrew Futreal, Zhenning Wang, Xiangdong Cheng, Jaffer A. Ajani, Linghua Wang

Issue&Volume: 2023-07-06

Abstract: Understanding tumor microenvironment (TME) reprogramming in gastric adenocarcinoma(GAC) progression may uncover novel therapeutic targets. Here, we performed single-cellprofiling of precancerous lesions, localized and metastatic GACs, identifying alterationsin TME cell states and compositions as GAC progresses. Abundant IgA+ plasma cells exist in the premalignant microenvironment, whereas immunosuppressivemyeloid and stromal subsets dominate late-stage GACs. We identified six TME ecotypes(EC1-6). EC1 is exclusive to blood, while EC4, EC5, and EC2 are highly enriched inuninvolved tissues, premalignant lesions, and metastases, respectively. EC3 and EC6,two distinct ecotypes in primary GACs, associate with histopathological and genomiccharacteristics, and survival outcomes. Extensive stromal remodeling occurs in GACprogression. High SDC2 expression in cancer-associated fibroblasts (CAFs) is linked to aggressive phenotypesand poor survival, and SDC2 overexpression in CAFs contributes to tumor growth. Our study provides a high-resolutionGAC TME atlas and underscores potential targets for further investigation.

DOI: 10.1016/j.ccell.2023.06.005

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00215-5

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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