Open AccessTERT mutations correlate with higher TMB value and unique tumor microenvironment and may be a potential biomarker for anti‐CTLA4 treatment
Author(s) -
Li Huahua,
Li Jia,
Zhang Chenyue,
Zhang Chenxing,
Wang Haiyong
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.3376
Subject(s) - immune system , tumor microenvironment , cancer research , cytotoxic t cell , immunotherapy , immunology , biology , telomerase reverse transcriptase , biomarker , tumor infiltrating lymphocytes , telomerase , genetics , gene , in vitro
Abstract Immune checkpoint inhibitors ( ICIs ) have recently changed therapeutic paradigms for patients across multiple cancer types. However, current biomarkers cannot accurately predict responses to ICIs . Telomerase reverse transcriptase ( TERT ) 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 ( TMB ) value, neoantigen load, and tumor purity. Lymphocyte infiltration, macrophage regulation, interferon‐gamma ( IFN‐γ ) response, and transforming growth factor‐β ( TGF‐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 ( anti‐CTLA4 ) 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.