Liver metastases across cancer types sharing tumor environment immunotolerance can impede immune response therapy and immune monitoring

Yuzhen Gao; Shipeng Chen; Hao Wang; Chenghao Wu; Rui An; Guoli Li; Min Yang; Ying Zhou; Yundong Zhou; Xinyou Xie; Hong Yu; Jun Zhang

Journal of Advanced Research (Jul 2024)

Liver metastases across cancer types sharing tumor environment immunotolerance can impede immune response therapy and immune monitoring

Yuzhen Gao,
Shipeng Chen,
Hao Wang,
Chenghao Wu,
Rui An,
Guoli Li,
Min Yang,
Ying Zhou,
Yundong Zhou,
Xinyou Xie,
Hong Yu,
Jun Zhang

Affiliations

Yuzhen Gao: Department of Clinical Laboratory, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, China
Shipeng Chen: Department of Laboratory Medicine, Xiamen Key Laboratory of Genetic Testing, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China; School of Clinical Medicine, Fujian Medical University, Fuzhou, China
Hao Wang: Department of Gastroenterology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Chenghao Wu: Department of Clinical Laboratory, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, China
Rui An: Department of Clinical Laboratory, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, China
Guoli Li: Department of Clinical Laboratory, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, China
Min Yang: Department of Clinical Laboratory, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, China
Ying Zhou: Department of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People's Hospital, Cancer Center, Zhejiang University School of Medicine, Hangzhou, China
Yundong Zhou: Shanghai Medical Innovation Fusion Biomedical Research Center, Shanghai, China
Xinyou Xie: Department of Clinical Laboratory, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, China
Hong Yu: Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Corresponding authors at: Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Qingchun East Road, Jianggan District, Hangzhou 310016, Zhejiang, China (J. Zhang and H, Yu).
Jun Zhang: Department of Clinical Laboratory, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, China; Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Hangzhou, Zhejiang, China; Corresponding authors at: Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Qingchun East Road, Jianggan District, Hangzhou 310016, Zhejiang, China (J. Zhang and H, Yu).

Journal volume & issue: Vol. 61
pp. 151 – 164

Abstract

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Background: Hepatic immune tolerance might contribute to the development of therapeutic resistance to immunotherapy. However, addressing this issue is challenging since the efficacy of immunotherapy in the context of liver metastasis (LM) remains poorly studied. Here, we aimed to establish an LM common immune feature (LMCIF) score to quantify the characteristics of LM immunotolerance across cancer types for assisting clinical disease management. Methods: Large-scale clinical data were collected to identify the prognosis of LM. Multi-omics datasets of metastatic cancers with LM special immune-related pathways (LMSIPs) from the Molecular Signatures Database (MSigDB) were used to obtain an LMCIF cluster. Based on differential expression genes (DEGs), a novel LMCIF score for the LMCIF cluster was constructed. In addition, multi-omics, and immunohistochemistry (IHC) data from the public and in-house cohorts were used to explore the features of LM, and LMCIF score. Results: Patients with LM had a worse prognosis and significantly lower infiltration of immune cells than patients with metastasis to other organs when analyzed with combined clinical and RNA sequencing data. After extracting the LMCIF cluster from 373 samples by utilizing 29 LMSIPs and validating them in a microarray cohort, an LMCIF score was established to confirm the role of the immunosuppressive environment as a contributor to the poor prognosis of LM across cancer types. Moreover, this LMCIF score could be used to predict the immune response of cancer patients undergoing immunotherapy. Finally, we identified that the majority of the 31 LMCIF genes exhibited a negative correlation with TME cells in LM patients, one of them, KRT19, which possessed the strongest positive correlation with LMCIF score, was confirmed to have an immunosuppressive effect through IHC analysis. Conclusions: Our results suggest that LM across cancer types share similar immunological profiles that induce immunotolerance and escape from immune monitoring. The novel LMCIF score represents a common liver metastasis immune cluster for predicting immunotherapy response, the results of which might benefit clinical disease management.

Published in Journal of Advanced Research

ISSN: 2090-1232 (Print); 2090-1224 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General); Science: Science (General)
Website: http://www.journals.elsevier.com/journal-of-advanced-research/

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