The Love-Hate Relationship Between TGF-β Signaling and the Immune System During Development and Tumorigenesis

被引：28
作者：
Chen, Baode [1 ]
Mu, Chenglin [2 ]
Zhang, Zhiwei [2 ]
He, Xuelin [3 ]
Liu, Xia [2 ]
机构：
[1] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Dept Lab Med, Hangzhou, Peoples R China
[2] Zhejiang Univ ZJU Hangzhou Global Sci, Inst Intelligent Bio Chem Mfg iBCM, Technol Innovat Ctr, Hangzhou, Peoples R China
[3] Zhejiang Univ, Affiliated Hosp 1, Coll Med, Kidney Dis Ctr, Hangzhou, Peoples R China
来源：
FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷
关键词：
TGF-beta; immune system; tumor progression; tumor microenvironment; cancer therapy; GROWTH-FACTOR-BETA; HEMATOPOIETIC STEM-CELLS; T-CELL; TRANSFORMING GROWTH-FACTOR-BETA-1; MYELOID CELLS; TUMOR-GROWTH; NK CELLS; CANCER; RECEPTOR; EXPRESSION;
D O I：
10.3389/fimmu.2022.891268
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Since TGF-beta was recognized as an essential secreted cytokine in embryogenesis and adult tissue homeostasis a decade ago, our knowledge of the role of TGF-beta in mammalian development and disease, particularly cancer, has constantly been updated. Mounting evidence has confirmed that TGF-beta is the principal regulator of the immune system, as deprivation of TGF-beta signaling completely abrogates adaptive immunity. However, enhancing TGF-beta signaling constrains the immune response through multiple mechanisms, including boosting Treg cell differentiation and inducing CD8(+) T-cell apoptosis in the disease context. The love-hate relationship between TGF-beta signaling and the immune system makes it challenging to develop effective monotherapies targeting TGF-beta, especially for cancer treatment. Nonetheless, recent work on combination therapies of TGF-beta inhibition and immunotherapy have provide insights into the development of TGF-beta-targeted therapies, with favorable outcomes in patients with advanced cancer. Hence, we summarize the entanglement between TGF-beta and the immune system in the developmental and tumor contexts and recent progress on hijacking crucial TGF-beta signaling pathways as an emerging area of cancer therapy.
引用
收藏
页数：17
相关论文
共 171 条
[1]   INHIBITION OF TGFβ SIGNALING USING SB-505124 BLOCKS TH17 DIFFERENTIATION AND RESTORES THE TH17/TREG BALANCE IN VIVO, BUT DOES NOT SUPPRESS EXPERIMENTAL ARTHRITIS [J].
Aarts, J. ;
Van Caam, A. ;
Helsen, M. ;
Walgreen, B. ;
Vitters, E. ;
Van de Loo, F. ;
Van Lent, P. ;
Van der Kraan, P. ;
Koenders, M. .
ANNALS OF THE RHEUMATIC DISEASES, 2020, 79 :1337-1337
[2]  
Akhurst RJ, 2001, TRENDS CELL BIOL, V11, pS44, DOI 10.1016/S0962-8924(01)82259-5
[3]   Targeting the TGFβ signalling pathway in disease [J].
Akhurst, Rosemary J. ;
Hata, Akiko .
NATURE REVIEWS DRUG DISCOVERY, 2012, 11 (10) :790-811
[4]  
[Anonymous], 2021, LANCET ONCOL, V22, P893, DOI 10.1016/S1470-2045(21)00353-3
[5]   TCR signaling intensity controls CD8+ T cell responsiveness to TGF-β [J].
Arumugam, Vidhyalakshmi ;
Bluemn, Theresa ;
Wesley, Erin ;
Schmidt, Amanda M. ;
Kambayashi, Taku ;
Malarkannan, Subramaniam ;
Riese, Matthew J. .
JOURNAL OF LEUKOCYTE BIOLOGY, 2015, 98 (05) :703-712
[6]   A Unidirectional Transition from Migratory to Perivascular Macrophage Is Required for Tumor Cell Intravasation [J].
Arwert, Esther N. ;
Harney, Allison S. ;
Entenberg, David ;
Wang, Yarong ;
Sahai, Erik ;
Pollard, Jeffrey W. ;
Condeelis, John S. .
CELL REPORTS, 2018, 23 (05) :1239-1248
[7]   Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer [J].
Bardeesy, Nabeel ;
Cheng, Kuang-hung ;
Berger, Justin H. ;
Chu, Gerald C. ;
Pahler, Jessica ;
Olson, Peter ;
Hezel, Aram F. ;
Horner, James ;
Lauwers, Gregory Y. ;
Hanahan, Douglas ;
DePinho, Ronald A. .
GENES & DEVELOPMENT, 2006, 20 (22) :3130-3146
[8]  
Batard P, 2000, J CELL SCI, V113, P383
[9]   Transforming Growth Factor-β Signaling in Immunity and Cancer [J].
Batlle, Eduard ;
Massague, Joan .
IMMUNITY, 2019, 50 (04) :924-940
[10]   IL1-Induced JAK/STAT Signaling Is Antagonized by TGFβ to Shape CAF Heterogeneity in Pancreatic Ductal Adenocarcinoma [J].
Biffi, Giulia ;
Oni, Tobiloba E. ;
Spielman, Benjamin ;
Hao, Yuan ;
Elyada, Ela ;
Park, Youngkyu ;
Preall, Jonathan ;
Tuveson, David A. .
CANCER DISCOVERY, 2019, 9 (02) :282-301
12345678910