Comprehensive single-cell analysis reveals mast cells' roles in cancer immunity

Hao Qian^#^{1

2

3}, Wenbo Wang^#⁴, Jiaomeng Pan^#⁵, Ming Zhao^#^{6

7}, Li Gao⁸, Jia Zeng⁹, Hang Gong¹⁰, Guangyan Zhangyuan^{1

2

3}, Zi Li¹¹, Mao Zhang⁵, Xia Shen¹², Yuanchi Weng^{13

14

15}, Xiaxing Deng^{16

17

18}, Yingying Huang¹⁹

Affiliations

¹ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Pancreatic Neoplasms Translational Research, Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China.
³ Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, China.
⁴ Department of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Yu-Yue Pathology Scientific Research Center, Chongqing, China.
⁷ Jinfeng Laboratory, Chongqing, China.
⁸ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
⁹ Department of Urology, Hunan University of Medicine General Hospital, Huaihua, Hunan, China.
¹⁰ Department of Hepatobiliary Surgery, Hunan University of Medicine General Hospital, Huaihua, Hunan, China.
¹¹ CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai, China.
¹² Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xiashen@sjtu.edu.cn.
¹³ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. wyuanchi@126.com.
¹⁴ Shanghai Key Laboratory of Pancreatic Neoplasms Translational Research, Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China. wyuanchi@126.com.
¹⁵ Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, China. wyuanchi@126.com.
¹⁶ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. kejiadxx@hotmail.com.
¹⁷ Shanghai Key Laboratory of Pancreatic Neoplasms Translational Research, Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China. kejiadxx@hotmail.com.
¹⁸ Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, China. kejiadxx@hotmail.com.
¹⁹ Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China. huangyingying@fudan.edu.cn.

^# Contributed equally.

PMID: 41073552
DOI: 10.1038/s41388-025-03590-y

Comprehensive single-cell analysis reveals mast cells' roles in cancer immunity

Hao Qian et al. Oncogene. 2025 Nov.

. 2025 Nov;44(45):4427-4439.

doi: 10.1038/s41388-025-03590-y. Epub 2025 Oct 10.

Authors

Affiliations

¹ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
² Shanghai Key Laboratory of Pancreatic Neoplasms Translational Research, Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China.
³ Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, China.
⁴ Department of Orthopedic Surgery, Shanghai Institute of Microsurgery on Extremities, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁵ Department of Liver Surgery and Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
⁶ Yu-Yue Pathology Scientific Research Center, Chongqing, China.
⁷ Jinfeng Laboratory, Chongqing, China.
⁸ CAS Key Laboratory of Computational Biology, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China.
⁹ Department of Urology, Hunan University of Medicine General Hospital, Huaihua, Hunan, China.
¹⁰ Department of Hepatobiliary Surgery, Hunan University of Medicine General Hospital, Huaihua, Hunan, China.
¹¹ CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai, China.
¹² Center for Single-Cell Omics, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. xiashen@sjtu.edu.cn.
¹³ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. wyuanchi@126.com.
¹⁴ Shanghai Key Laboratory of Pancreatic Neoplasms Translational Research, Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China. wyuanchi@126.com.
¹⁵ Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, China. wyuanchi@126.com.
¹⁶ Department of General Surgery, Pancreatic Disease Center, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. kejiadxx@hotmail.com.
¹⁷ Shanghai Key Laboratory of Pancreatic Neoplasms Translational Research, Research Institute of Pancreatic Diseases, Shanghai Jiaotong University School of Medicine, Shanghai, China. kejiadxx@hotmail.com.
¹⁸ Institute of Translational Medicine, Shanghai Jiaotong University, Shanghai, China. kejiadxx@hotmail.com.
¹⁹ Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai, China. huangyingying@fudan.edu.cn.

^# Contributed equally.

PMID: 41073552
DOI: 10.1038/s41388-025-03590-y

Abstract

Mast cells, traditionally known for their roles in allergic reactions and pathogen defense, have been revealed to possess significant functional diversity within the tumor microenvironment (TME). Through single-cell RNA sequencing analysis across 15 solid tumors (385 samples from 264 patients), 10 distinct mast cell states characterized by unique gene expression patterns and functional attributes were identified. Notably, the C7-HLA-DR cluster that closely linked with antigen presentation, has emerged as a key player in shaping anti-tumor immune responses. In this study, systematic analysis demonstrated that the C7-HLA-DR cluster could interact with T cells to enhance the efficacy of immunotherapy and improve patients' prognosis. On the contrary, the C1-HSPA1 cluster exhibited pro-tumor characteristics, highlighting the functional diversity of mast cells within TME. These findings illustrate the landscape of mast cell within TME and propose a new avenue to boost the efficacy of immunotherapy.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethical approval: The study was approved by the Research Ethics Committee of Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University and conducted in accordance with the Declaration of Helsinki. All subjects gave written informed consent before participating in the study.

References

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Comprehensive single-cell analysis reveals mast cells' roles in cancer immunity

Affiliations

Comprehensive single-cell analysis reveals mast cells' roles in cancer immunity

Authors

Affiliations

Abstract

Conflict of interest statement

References

MeSH terms

Substances

LinkOut - more resources

Full Text Sources

Medical

Research Materials

Miscellaneous