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作者

Huahua Li Jia Li Chenyue Zhang Chenxing Zhang Haiyong Wang

作者单位

Department of Integrated Therapy, Fudan University Shanghai Cancer Center, Shanghai Medical College, Shanghai, China Department of Nephrology, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China Haiyong Wang, Department of Internal Medicine-Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan 250117, China. Department of Internal Medicine‐Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China Department of Integrated Chinese and Western Medicine, Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China

刊名

Cancer Medicine

年份

2020

卷号

Vol.9 No.19

页码

7151-7160

ISSN

2045-7634

关键词

anti‐CTLA4 treatment immune cells infiltration melanoma TERT mutation TMB

摘要

Immune checkpoint inhibitors have recently changed therapeutic paradigms for patients across multiple cancer types. However, current biomarkers cannot accurately predict responses to ICIs. Telomerase reverse transcriptase mutations lead to an aberrant upregulation of TERT expression, and ultimately allow telomere maintenance, thus supporting immortalization of cancer cells. This study aimed to investigate whether the TERT mutation is a potential predictor of ICI treatment across all cancer typ...更多

Immune checkpoint inhibitors have recently changed therapeutic paradigms for patients across multiple cancer types. However, current biomarkers cannot accurately predict responses to ICIs. Telomerase reverse transcriptase mutations lead to an aberrant upregulation of TERT expression, and ultimately allow telomere maintenance, thus supporting immortalization of cancer cells. This study aimed to investigate whether the TERT mutation is a potential predictor of ICI treatment across all cancer types. TERT mutations positively correlated with a higher tumor mutational burden value, neoantigen load, and tumor purity. Lymphocyte infiltration, macrophage regulation, interferon‐gamma response, and transforming growth factor‐β response which was representative immune‐expression signatures, all had higher signature scores in the TERT mutation group. Activated CD4 T cell, naïve B cell, activated dendritic cell, M0 macrophage, M1 macrophage, neutrophil, resting NK cell, and plasma cells all had relatively higher immune scores in the TERT mutation group, whereas Th series cells, memory B cell, resting mast cells, monocytes, and activated NK cells had lower immune scores. Notably, in the subgroup analysis of monotherapy and combination ICI treatment, only in the anti‐cytotoxic‐T‐lymphocyte‐associated antigen 4 group, patients with TERT mutations had a better prognosis, especially for melanoma. Therefore, TERT mutations were closely related to a higher TMB value and unique tumor microenvironment, which may be the reason that TERT mutations may be a potential biomarker for anti‐CTLA4 treatment.收起

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