OncoTargets and Therapy (Nov 2019)
Blocking TGF-β Signaling To Enhance The Efficacy Of Immune Checkpoint Inhibitor
Abstract
Xianguang Bai,1,2,* Ming Yi,2,* Ying Jiao,2 Qian Chu,2 Kongming Wu2,3 1Medical School, Pingdingshan University, Pingdingshan, Henan, People’s Republic of China; 2Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Kongming Wu; Qian ChuDepartment of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, People’s Republic of ChinaEmail [email protected]; [email protected]: During malignant transformation, a growing body of mutations accumulate in cancer cells which not only drive cancer progression but also endow cancer cells with high immunogenicity. However, because one or multiple steps in cancer-immunity cycle are impaired, anti-cancer immune response is too weak to effectively clear cancer cells. Therefore, how to restore robust immune response to malignant cells is a hot research topic in cancer therapeutics field. In the last decade, based on the deeper understanding of cancer immunity, great signs of progress have been made in cancer immunotherapies especially immune checkpoint inhibitors (ICIs). ICIs could block negative immune co-stimulatory pathways and reactivate tumor-infiltrating lymphocytes (TILs) from exhausted status. ICIs exhibit potent anti-cancer effect and have been approved for the treatment of numerous cancer types. Parallel with durable and effective tumor control, the actual response rate of ICIs is unsatisfactory. Although a subset of patients benefit from ICIs treatment, a large proportion of patients show primary or acquired resistance. Previously intensive studies indicated that the efficacy of ICIs was determined by a series of factors including tumor mutation burden, programmed death ligand-1 (PD-L1) expression, and TILs status. Recently, it was reported that transforming growth factor-beta (TGF-β) signaling pathway participated in cancer immune escape and ICI resistance. Concurrent TGF-β blockade might be a feasible strategy to enhance the efficacy of immunotherapy and relieve ICI resistance. In this mini-review, we summarized the latest understanding of TGF-β signaling pathway and cancer immunity. Besides, we highlighted the synergistic effect of TGF-β blockade and ICIs.Keywords: immunotherapy, immune checkpoint inhibitor, PD-1, PD-L1, TGF-β, tumor immune microenvironment, tumor infiltrating lymphocyte
