TY - JOUR
T1 - Evolution of immune and stromal cell states and ecotypes during gastric adenocarcinoma progression
AU - Wang, Ruiping
AU - Song, Shumei
AU - Qin, Jiangjiang
AU - Yoshimura, Katsuhiro
AU - Peng, Fuduan
AU - Chu, Yanshuo
AU - Li, Yuan
AU - Fan, Yibo
AU - Jin, Jiankang
AU - Dang, Minghao
AU - Dai, Enyu
AU - Pei, Guangsheng
AU - Han, Guangchun
AU - Hao, Dapeng
AU - Li, Yating
AU - Chatterjee, Deyali
AU - Harada, Kazuto
AU - Pizzi, Melissa Pool
AU - Scott, Ailing W.
AU - Tatlonghari, Ghia
AU - Yan, Xinmiao
AU - Xu, Zhiyuan
AU - Hu, Can
AU - Mo, Shaowei
AU - Shanbhag, Namita
AU - Lu, Yang
AU - Sewastjanow-Silva, Matheus
AU - Fouad Abdelhakeem, Ahmed Adel
AU - Peng, Guang
AU - Hanash, Samir M.
AU - Calin, George A.
AU - Yee, Cassian
AU - Mazur, Pawel
AU - Marsden, Autumn N.
AU - Futreal, Andrew
AU - Wang, Zhenning
AU - Cheng, Xiangdong
AU - Ajani, Jaffer A.
AU - Wang, Linghua
N1 - Publisher Copyright:
© 2023 Elsevier Inc.
PY - 2023/8/14
Y1 - 2023/8/14
N2 - 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.
AB - 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.
KW - Cancer-associated fibroblast
KW - Chronic Atrophic Gastritis
KW - Ecotype
KW - Gastric Adenocarcinoma
KW - Immune-Stroma Crosstalk
KW - Intestinal Metaplasia
KW - Peritoneal Carcinomatosis
KW - Single Cell RNA Sequencing
KW - Syndecan 2
KW - Tumor Microenvironment
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U2 - 10.1016/j.ccell.2023.06.005
DO - 10.1016/j.ccell.2023.06.005
M3 - Article
C2 - 37419119
AN - SCOPUS:85167451635
SN - 1535-6108
VL - 41
SP - 1407-1426.e9
JO - Cancer cell
JF - Cancer cell
IS - 8
ER -