Spatial transcriptome unveils a discontinuous inflammatory pattern in proficient mismatch repair colorectal adenocarcinoma

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  • Rongxin Zhang
  • Yu Feng
  • Wenjuan Ma
  • Yanying Guo
  • Mei Luo
  • Young Li
  • Yupeng Zang
  • Xuan Dong
  • Shixun Lu
  • Qiang Guo
  • Qumiao Xu
  • Huanyi Chen
  • Yijian Li
  • Longqi Liu
  • CHEN, Ao
  • Gong Chen
  • Xun Xu

The preexistence of immune cells in the tumor microenvironment substantiates the efficacy of immunotherapy in cancer patients. Although the complex intratumoral immune heterogeneity has been extensively studied in single cell resolution, hi-res spatial investigations are limited. In this study, we performed a spatial transcriptome analysis of 4 colorectal adenocarcinoma specimens and 2 paired distant normal specimens to identify the molecular pattern involved in a discontinuous inflammatory response in pathologically annotated cancer regions. Based on the location of spatially varied gene expression, we unmasked the spatially-varied immune ecosystem and identified the locoregional “warmed-up” immune response in predefined “cold” tumor with substantial infiltration of immune components. This “warmed-up” immune profile was found to be associated with the in-situ copy number variance and the tissue remodeling process. Further, “warmed-up” signature genes indicated improved overall survival in CRC patients obtained from TCGA database.

OriginalsprogEngelsk
TidsskriftFundamental Research
Vol/bind3
Udgave nummer4
Antal sider7
ISSN2667-3258
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
Wenjuan Ma is an attending doctor in Intensive Care Unit of Sun Yat-sen University. Her research interest focused on immunotherapy and microenvironment of malignant tumor. Her research was supported by National Natural Science Foundation of China and China Postdoctoral Science Foundation.

Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (Grant No. 82002628 ), Natural Science Foundation of Guangdong Province (Grant No. 2021A1515010096 ), China Postdoctoral Science Foundation (Grant No. 2019M660227 ), Chinese Society of Clinical Oncology Foundation (Grant Nos. Y-HR2018-319 , Y-L2017-002 , and Y-JS2019-009 ), Sun Yat-sen University Basic Research Fund (Grant No. 19ykpy180 ), and the open research funds from the Sixth Affiliated Hospital of Guangzhou Medical University , Qingyuan People's Hospital ( 202011-103 ).

Funding Information:
Dr. Longqi Liu is the director of Institute of Cell Science of BGI-Research. His major focus is genetics and transcriptomics and his research has been published by top scientific journals including Cell, Nature, etc. He also managed funds from National Natural Science Foundation of China.

Funding Information:
Dr. Rongxin Zhang is a deputy chief surgeon of colorectal cancer in Sun Yat-sen University Cancer Center. His research interests focus on the clinical efficacy of chemotherapy, immunotherapy, cancer metastasis and related mechanistic study in colorectal cancer. Dr. Zhang also managed 5 research grants including National Natural Science Funds and Guangdong Natural Science Funds.

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© 2022

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