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

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

doi:10.1016/j.ccell.2023.06.005

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

Cancer Cell. 2023 Aug 14;41(8):1407-1426.e9. doi: 10.1016/j.ccell.2023.06.005. Epub 2023 Jul 6.

Authors

Ruiping Wang¹, Shumei Song², Jiangjiang Qin³, Katsuhiro Yoshimura², Fuduan Peng¹, Yanshuo Chu¹, Yuan Li⁴, Yibo Fan², Jiankang Jin², Minghao Dang¹, Enyu Dai¹, Guangsheng Pei¹, Guangchun Han¹, Dapeng Hao¹, Yating Li⁵, Deyali Chatterjee⁶, Kazuto Harada², Melissa Pool Pizzi², Ailing W Scott², Ghia Tatlonghari², Xinmiao Yan¹, Zhiyuan Xu⁷, Can Hu⁷, Shaowei Mo⁷, Namita Shanbhag², Yang Lu⁸, Matheus Sewastjanow-Silva², Ahmed Adel Fouad Abdelhakeem², Guang Peng⁹, Samir M Hanash⁹, George A Calin¹⁰, Cassian Yee¹¹, Pawel Mazur¹², Autumn N Marsden¹, Andrew Futreal¹, Zhenning Wang⁴, Xiangdong Cheng³, Jaffer A Ajani¹³, Linghua Wang¹⁴

Affiliations

¹ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
² Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
³ Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China; Institute of Basic Medicine and Cancer, Chinese Academy of Sciences, Hangzhou, Zhejiang 310018, China.
⁴ Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, Shenyang 110001, China.
⁵ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁶ Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁷ Department of Gastric Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, China.
⁸ Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
⁹ Department of Clinical Cancer Prevention, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹⁰ Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹¹ Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹² Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
¹³ Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: jajani@mdanderson.org.
¹⁴ Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; The University of Texas MD Anderson Cancer Center UTHealth Houston Graduate School of Biomedical Sciences (GSBS), Houston, TX 77030, USA. Electronic address: lwang22@mdanderson.org.

PMID: 37419119
PMCID: PMC10528152 (available on 2024-08-14)
DOI: 10.1016/j.ccell.2023.06.005

Abstract

Understanding tumor microenvironment (TME) reprogramming in gastric adenocarcinoma (GAC) progression may uncover novel therapeutic targets. Here, we performed single-cell profiling of precancerous lesions, localized and metastatic GACs, identifying alterations in TME cell states and compositions as GAC progresses. Abundant IgA⁺ plasma cells exist in the premalignant microenvironment, whereas immunosuppressive myeloid 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 in uninvolved tissues, premalignant lesions, and metastases, respectively. EC3 and EC6, two distinct ecotypes in primary GACs, associate with histopathological and genomic characteristics, and survival outcomes. Extensive stromal remodeling occurs in GAC progression. High SDC2 expression in cancer-associated fibroblasts (CAFs) is linked to aggressive phenotypes and poor survival, and SDC2 overexpression in CAFs contributes to tumor growth. Our study provides a high-resolution GAC TME atlas and underscores potential targets for further investigation.

Keywords: Cancer-associated fibroblast; Chronic Atrophic Gastritis; Ecotype; Gastric Adenocarcinoma; Immune-Stroma Crosstalk; Intestinal Metaplasia; Peritoneal Carcinomatosis; Single Cell RNA Sequencing; Syndecan 2; Tumor Microenvironment.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adenocarcinoma* / pathology
Cancer-Associated Fibroblasts* / pathology
Ecotype
Humans
Precancerous Conditions* / pathology
Stomach Neoplasms* / genetics
Stomach Neoplasms* / metabolism
Stromal Cells / pathology
Tumor Microenvironment

Abstract

Publication types

MeSH terms

Grants and funding