Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis

Hashimoto, Masahiro; Kojima, Yasuhiro; Sakamoto, Takeharu; Ozato, Yuki; Nakano, Yusuke; Abe, Tadashi; Hosoda, Kiyotaka; Saito, Hideyuki; Higuchi, Satoshi; Hisamatsu, Yuichi; Toshima, Takeo; Yonemura, Yusuke; Masuda, Takaaki; Hata, Tsuyoshi; Nagayama, Satoshi; Kagawa, Koichi; Goto, Yasuhiro; Utou, Mitsuaki; Gamachi, Ayako; Imamura, Kiyomi; Kuze, Yuta; Zenkoh, Junko; Suzuki, Ayako; Takahashi, Kazuki; Niida, Atsushi; Hirose, Haruka; Hayashi, Shuto; Koseki, Jun; Fukuchi, Satoshi; Murakami, Kazunari; Yoshizumi, Tomoharu; Kadomatsu, Kenji; Tobo, Taro; Oda, Yoshinao; Uemura, Mamoru; Eguchi, Hidetoshi; Doki, Yuichiro; Mori, Masaki; Oshima, Masanobu; Shibata, Tatsuhiro; Suzuki, Yutaka; Shimamura, Teppei; Mimori, Koshi

doi:10.1016/j.ebiom.2024.105102

eBioMedicine

2024

DOI: 10.1016/j.ebiom.2024.105102

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Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis

Masahiro Hashimoto,

Yasuhiro Kojima,

Takeharu Sakamoto

et al.

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Cited by 3 publications

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Immune escape between endoplasmic reticulum stress-related cancer cells and exhausted CD8+T cells leads to neoadjuvant chemotherapy resistance in ovarian cancer

Zhang,

Song

et al. 2024

Biochemical and Biophysical Research Communications

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Immune escape between endoplasmic reticulum stress-related cancer cells and exhausted CD8+T cells leads to neoadjuvant chemotherapy resistance in ovarian cancer

Zhang,

Song

et al. 2024

Biochemical and Biophysical Research Communications

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Spatial omics technologies for understanding molecular status associated with cancer progression

Nagasawa,

Zenkoh,

Suzuki

et al. 2024

Cancer Science

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Cancer cells are generally exposed to numerous extrinsic stimulations in the tumor microenvironment. In this environment, cancer cells change their expression profiles to fight against circumstantial stresses, allowing their progression in the challenging tissue space. Technological advancements of spatial omics have had substantial influence on cancer genomics. This technical progress, especially that occurring in the spatial transcriptome, has been drastic and rapid. Here, we describe the latest spatial analytical technologies that have allowed omics feature characterization to retain their spatial and histopathological information in cancer tissues. Several spatial omics platforms have been launched, and the latest platforms finally attained single‐cell level or even higher subcellular level resolution. We discuss several key papers elucidating the initial utility of the spatial analysis. In fact, spatial transcriptome analyses reveal comprehensive omics characteristics not only in cancer cells but also their surrounding cells, such as tumor infiltrating immune cells and cancer‐associated fibroblasts. We also introduce several spatial omics platforms. We describe our own attempts to investigate molecular events associated with cancer progression. Furthermore, we discuss the next challenges in analyzing the multiomics status of cells, including their morphology and location. These novel technologies, in conjunction with spatial transcriptome analysis and, more importantly, with histopathology, will elucidate even novel key aspects of the intratumor heterogeneity of cancers. Such enhanced knowledge is expected to open a new path for overcoming therapeutic resistance and eventually to precisely stratify patients.

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HMGB2 drives tumor progression and shapes the immunosuppressive microenvironment in hepatocellular carcinoma: insights from multi-omics analysis

Chen,

Meng,

Xiang

2024

Front. Immunol.

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BackgroundHepatocellular carcinoma (HCC) poses a significant health burden globally, with high mortality rates despite various treatment options. Immunotherapy, particularly immune-checkpoint inhibitors (ICIs), has shown promise, but resistance and metastasis remain major challenges. Understanding the intricacies of the tumor microenvironment (TME) is imperative for optimizing HCC management strategies and enhancing patient prognosis.MethodsThis study employed a comprehensive approach integrating multi-omics approaches, including single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing (Bulk RNA-seq), and validation in clinical samples using spatial transcriptomics (ST) and multiplex immunohistochemistry (mIHC). The analysis aimed to identify key factors influencing the immunosuppressive microenvironment associated with HCC metastasis and immunotherapy resistance.ResultsHMGB2 is significantly upregulated in HCCTrans, a transitional subgroup associated with aggressive metastasis. Furthermore, HMGB2 expression positively correlates with an immunosuppressive microenvironment, particularly evident in exhausted T cells. Notably, HMGB2 expression correlated positively with immunosuppressive markers and poor prognosis in HCC patients across multiple cohorts. ST combined with mIHC validated the spatial expression patterns of HMGB2 within the TME, providing additional evidence of its role in HCC progression and immune evasion.ConclusionHMGB2 emerges as a critical player of HCC progression, metastasis, and immunosuppression. Its elevated expression correlates with aggressive tumor behavior and poor patient outcomes, suggesting its potential as both a therapeutic target and a prognostic indicator in HCC management.

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Spatial and single-cell colocalisation analysis reveals MDK-mediated immunosuppressive environment with regulatory T cells in colorectal carcinogenesis

Cited by 3 publications

References 80 publications

Immune escape between endoplasmic reticulum stress-related cancer cells and exhausted CD8+T cells leads to neoadjuvant chemotherapy resistance in ovarian cancer

Immune escape between endoplasmic reticulum stress-related cancer cells and exhausted CD8+T cells leads to neoadjuvant chemotherapy resistance in ovarian cancer

Spatial omics technologies for understanding molecular status associated with cancer progression

HMGB2 drives tumor progression and shapes the immunosuppressive microenvironment in hepatocellular carcinoma: insights from multi-omics analysis

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