1. Dual anti-PD-(L)1/TGF-β inhibitors in cancer immunotherapy – Updated.
- Author
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Karami, Zana, Mortezaee, Keywan, and Majidpoor, Jamal
- Subjects
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PROGRAMMED cell death 1 receptors , *IMMUNE checkpoint inhibitors , *TRANSFORMING growth factors , *REGULATORY T cells , *CHIMERIC proteins , *HUMAN papillomavirus - Abstract
• TGF-β promotes anti-tumor immune cell exclusion and dysfunction. • TGF-β and PD-L1 show independent but complementary immunosuppressive potentials. • Anti-PD-L1/TGF-βRII trap agents enable PD-L1 saturation and TGF-β sequestration. • M7824 is more effective in PD-L1high or immune-excluded tumors. Immune checkpoint inhibitor (ICI) therapy suffers from tumor resistance and relapse in majority of patients due to the suppressive tumor immune microenvironment (TIME). Advances in the field have brought about development of fusion proteins able to target two signaling simultaneously and to exert maximal anti-cancer immunity. Bispecific inhibitors of transforming growth factor (TGF)-β signaling and programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) are developed to reduce the rate of relapse and to achieve durable anti-cancer therapy. TGF-β is well-known for its immunosuppressive activity, and it takes critical roles in promotion of all tumor hallmarks. Bispecific anti-PD-(L)1/TGF-β inhibitors reinvigorate effector activity of CD8+ T and natural killer (NK) cells, hamper regulatory T cell (Treg) expansion, and increase the density of anti-tumor type 1 macrophages (M1). Responses to the bispecific approach are higher compared with solo anti-PD-(L)1 or TGF-β targeted therapy, and are seemingly more pronounced in human papillomavirus (HPV)+ patients. High expression of PD-L1 or immune-excluded phenotype in a tumor can also be markers of better response to the bispecific strategy. Besides, anti-PD-(L)1/TGF-β inhibitor therapy can be used safely with other therapeutic modalities including vaccination, radiation and chemotherapy. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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