The Web-Based Portal SpatialTME Integrates Histological Images with Single-Cell and Spatial Transcriptomics to Explore the Tumor Microenvironment

Author:

Shi Jintong1ORCID,Wei Xia1ORCID,Xun Zhenzhen1ORCID,Ding Xinyu1ORCID,Liu Yao234ORCID,Liu Lianxin234ORCID,Ye Youqiong1ORCID

Affiliation:

1. 1Center for Immune-Related Diseases at Shanghai Institute of Immunology, Ruijin Hospital, State Key Laboratory of Systems Medicine for Cancer, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China.

2. 2Division of Life Sciences and Medicine, Department of Hepatobiliary Surgery, Centre for Leading Medicine and Advanced Technologies of IHM, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, China.

3. 3Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, Hefei, Anhui, China.

4. 4Anhui Provincial Clinical Research Center for Hepatobiliary Diseases, Hefei, Anhui, China.

Abstract

Abstract The tumor microenvironment (TME) represents a complex network in which tumor cells communicate not only with each other but also with stromal and immune cells. The intercellular interactions in the TME contribute to tumor initiation, progression, metastasis, and treatment outcome. Recent advances in spatial transcriptomics (ST) have revolutionized the molecular understanding of the TME at the spatial level. A comprehensive interactive analysis resource specifically designed for characterizing the spatial TME could facilitate further advances using ST. In this study, we collected 296 ST slides covering 19 cancer types and developed a computational pipeline to delineate the spatial structure along the malignant–boundary–nonmalignant axis. The pipeline identified differentially expressed genes and their functional enrichment, deconvoluted the cellular composition of the TME, reconstructed cell type–specific gene expression profiles at the sub-spot level, and performed cell–cell interaction analysis. Finally, the user-friendly database SpatialTME (http://www.spatialtme.yelab.site/) was constructed to provide search, visualization, and downloadable results. These detailed analyses are able to reveal the heterogeneous regulatory network of the spatial microenvironment and elucidate associations between spatial features and tumor development or response to therapy, offering a valuable resource to study the complex TME. Significance: SpatialTME provides spatial structure, cellular composition, expression, function, and cell–cell interaction information to enable investigations into the tumor microenvironment at the spatial level to advance understanding of cancer development and treatment.

Funder

National Natural Science Foundation of China

National Key Research and Development Program of China

Shanghai Science and Technology Commission

Shanghai Jiao Tong University 2030 Initiative

the Research Funds of Centre for Leading Medicine and Advanced Technologies of IHM

Provincial Key R&D Programme of Anhui Province

the University Synergy Innovation Program of Anhui Province

Publisher

American Association for Cancer Research (AACR)

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