Formin protein DIAPH1 positively regulates PD-L1 expression and predicts the therapeutic response to anti-PD-1/PD-L1 immunotherapy

被引:15
作者
Mei, Jie [1 ,2 ]
Cai, Yun [2 ]
Wang, Huiyu [1 ]
Xu, Rui [3 ]
Zhou, Jiaofeng [4 ]
Lu, Jiahui [1 ]
Yang, Xuejing [1 ]
Pan, Jiadong [2 ]
Liu, Chaoying [1 ,5 ]
Xu, Junying [1 ,5 ]
Zhu, Yichao [4 ,6 ]
机构
[1] Nanjing Med Univ, Dept Oncol, Affiliated Wuxi Peoples Hosp, Wuxi 214023, Jiangsu, Peoples R China
[2] Nanjing Med Univ, Wuxi Coll Clin Med, Wuxi 214023, Jiangsu, Peoples R China
[3] Nanjing Med Univ, Coll Clin Med 1, Nanjing 211166, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Dept Physiol, Nanjing 211166, Jiangsu, Peoples R China
[5] Nanjing Med Univ, Dept Oncol, Affiliated Wuxi Peoples Hosp, 299 Qingyang Rd, Wuxi 214023, Peoples R China
[6] Nanjing Med Univ, Dept Physiol, 101 Longmian Av, Nanjing 211166, Peoples R China
基金
中国国家自然科学基金;
关键词
DIAPH1; PD-L1; TGF-?1; Immunotherapy; Biomarker; DIAPHANOUS-RELATED FORMINS; MESENCHYMAL TRANSITION; TGF-BETA; CANCER; CARCINOMA; INVASION; RECEPTOR; ESCAPE; FAMILY; CELLS;
D O I
10.1016/j.clim.2022.109204
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Formins are evolutionarily conserved genes and profoundly affect cancer progression. This study aims to explore the expressions, prognostic values, and immunological correlations of Formins in cancer. Specific Formins were dysregulated and immuno-biologically correlated in breast cancer (BRCA). Formins showed different expression patterns, namely some were enriched in immune cells while some were enriched in tumor cells. Among all Formins, DIAPH1 was enriched in tumor cells and associated with an inflamed tumor microenvironment (TME). DIAPH1 functioned as an oncogene in BRCA and mediated TGF-beta 1-induced epithelial-mesenchymal trans-formation (EMT) and PD-L1 expression. Moreover, DIAPH1 was overexpressed in most cancers and functioned as a novel pan-cancer immuno-marker, which could predict the response to anti-PD-1/PD-L1 immunotherapy. Overall, DIAPH1 functions as an oncogene and is immunologically correlated, which could be utilized as an alternative biomarker for predicting the immunotherapeutic response.
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页数:15
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共 49 条
[1]   Thymoquinone Anticancer Effects Through the Upregulation of NRF2 and the Downregulation of PD-L1 in MDA-MB-231 Triple-Negative Breast Cancer Cells [J].
Adinew, Getinet ;
Messeha, Samia S. ;
Badisa, Ramesh ;
Taka, Equar ;
Soliman, Karam F. A. .
FASEB JOURNAL, 2022, 36
[2]   Transforming Growth Factor-β Signaling in Immunity and Cancer [J].
Batlle, Eduard ;
Massague, Joan .
IMMUNITY, 2019, 50 (04) :924-940
[3]   Biomarkers for immune checkpoint inhibition in non-small cell lung cancer (NSCLC) [J].
Bodor, J. Nicholas ;
Boumber, Yanis ;
Borghaei, Hossein .
CANCER, 2020, 126 (02) :260-270
[4]   Interferon-Induced Transmembrane Protein 3 Shapes an Inflamed Tumor Microenvironment and Identifies Immuno-Hot Tumors [J].
Cai, Yun ;
Ji, Wenfei ;
Sun, Chuan ;
Xu, Rui ;
Chen, Xuechun ;
Deng, Yifan ;
Pan, Jiadong ;
Yang, Jiayue ;
Zhu, Hongjun ;
Mei, Jie .
FRONTIERS IN IMMUNOLOGY, 2021, 12
[5]   Force-induced Myofibroblast Differentiation through Collagen Receptors Is Dependent on Mammalian Diaphanous (mDia) [J].
Chan, Matthew W. C. ;
Chaudary, Faiza ;
Lee, Wilson ;
Copeland, John W. ;
McCulloch, Christopher A. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (12) :9273-9281
[6]   HMGB1 Enhances the AGE-Induced Expression of CTGF and TGF-β via RAGE-Dependent Signaling in Renal Tubular Epithelial Cells [J].
Cheng, Meichu ;
Liu, Hong ;
Zhang, Dongshan ;
Liu, Yinghong ;
Wang, Chang ;
Liu, Fuyou ;
Chen, Junxiang .
AMERICAN JOURNAL OF NEPHROLOGY, 2015, 41 (03) :257-266
[7]   MRTF-A-NF-κB/p65 axis-mediated PDL1 transcription and expression contributes to immune evasion of non-small-cell lung cancer via TGF-β [J].
Du, Fu ;
Qi, Xin ;
Zhang, Aotong ;
Sui, Fanfan ;
Wang, Xuemin ;
Proud, Christopher G. ;
Lin, Cunzhi ;
Fan, Xinglong ;
Li, Jing .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2021, 53 (09) :1366-1378
[8]   Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation [J].
Freeman, GJ ;
Long, AJ ;
Iwai, Y ;
Bourque, K ;
Chernova, T ;
Nishimura, H ;
Fitz, LJ ;
Malenkovich, N ;
Okazaki, T ;
Byrne, MC ;
Horton, HF ;
Fouser, L ;
Carter, L ;
Ling, V ;
Bowman, MR ;
Carreno, BM ;
Collins, M ;
Wood, CR ;
Honjo, T .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :1027-1034
[9]   Pembrolizumab for the Treatment of Non-Small-Cell Lung Cancer [J].
Garon, Edward B. ;
Rizvi, Naiyer A. ;
Hui, Rina ;
Leighl, Natasha ;
Balmanoukian, Ani S. ;
Eder, Joseph Paul ;
Patnaik, Amita ;
Aggarwal, Charu ;
Gubens, Matthew ;
Horn, Leora ;
Carcereny, Enric ;
Ahn, Myung-Ju ;
Felip, Enriqueta ;
Lee, Jong-Seok ;
Hellmann, Matthew D. ;
Hamid, Omid ;
Goldman, Jonathan W. ;
Soria, Jean-Charles ;
Dolled-Filhart, Marisa ;
Rutledge, Ruth Z. ;
Zhang, Jin ;
Lunceford, Jared K. ;
Rangwala, Reshma ;
Lubiniecki, Gregory M. ;
Roach, Charlotte ;
Emancipator, Kenneth ;
Gandhi, Leena .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (21) :2018-2028
[10]   The mir-200 family and mir-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1 [J].
Gregory, Philip A. ;
Bert, Andrew G. ;
Paterson, Emily L. ;
Barry, Simon C. ;
Tsykin, Anna ;
Farshid, Gelareh ;
Vadas, Mathew A. ;
Khew-Goodall, Yeesim ;
Goodall, Gregory J. .
NATURE CELL BIOLOGY, 2008, 10 (05) :593-601