Combination Therapy of Bispecific Protein of Anti-PD-L1 Fused with TGF- β Receptor in Cancer

Authors: Juntao Yu, Tingyan Zhang, Qingqing Zhou, Rong Tang, and Jianfei Yang*

DOI: 10.23880/aii-16000170

Volume 4, Issue 2

Abstract

Transforming growth factor β (TGF-β) and programmed death-ligand 1 (PD-L1) initiate signaling pathways with complementary, nonredundant immunosuppressive functions in the tumor microenvironment (TME). In the TME, dysregulated TGF-β signaling suppresses antitumor immunity and promotes cancer fibrosis, epithelial-mesenchymal transition, and angiogenesis. Meanwhile, PD-L1 expression inactivates cytotoxic T cell function and restricts immunosurveillance in the TME. Anti-PD-L1 therapies have been approved for the treatment of various cancers, while TGF-β signaling in the TME is associated with resistance to anti-PD-L1 therapies. Here, we have reviewed the rationale of the TGF-β and PD-L1 pathways in cancer and discussed current strategies using combination therapies that block these pathways separately or approaches with dual-targeting agents that may block the pathways simultaneously. Importantly, according to current clinical results, we propose the developing strategy of combination treatment with two or more agents.

Keywords: PD-L1; TGF-β; Cancer; Tumor Microenvironment; Combination Therapy

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