Next-generation immunotherapy for solid tumors: Combination immunotherapy with crosstalk blockade of TGFβ and PD-1/PD-L1 Review
| Authors: | Quach, H. T.; Hou, Z.; Bellis, R. Y.; Saini, J. K.; Amador-Molina, A.; Adusumilli, P. S.; Xiong, Y. |
| Review Title: | Next-generation immunotherapy for solid tumors: Combination immunotherapy with crosstalk blockade of TGFβ and PD-1/PD-L1 |
| Abstract: | Introduction: In solid tumor immunotherapy, less than 20% of patients respond to anti-programmed cell death 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) agents. The role of transforming growth factor β (TGFβ) in diverse immunity is well-established; however, systemic blockade of TGFβ is associated with toxicity. Accumulating evidence suggests the role of crosstalk between TGFβ and PD-1/PD-L1 pathways. Areas covered: We focus on TGFβ and PD-1/PD-L1 signaling pathway crosstalk and the determinant role of TGFβ in the resistance of immune checkpoint blockade. We provide the rationale for combination anti-TGFβ and anti-PD-1/PD-L1 therapies for solid tumors and discuss the current status of dual blockade therapy in preclinical and clinical studies. Expert opinion: The heterogeneity of tumor microenvironment across solid tumors complicates patient selection, treatment regimens, and response and toxicity assessment for investigation of dual blockade agents. However, clinical knowledge from single-agent studies provides infrastructure to translate dual blockade therapies. Dual TGFβ and PD-1/PD-L1 blockade results in enhanced T-cell infiltration into tumors, a primary requisite for successful immunotherapy. A bifunctional fusion protein specifically targets TGFβ in the tumor microenvironment, avoiding systemic toxicity, and prevents interaction of PD-1+ cytotoxic cells with PD-L1+ tumor cells. © 2022 Informa UK Limited, trading as Taylor & Francis Group. |
| Keywords: | signal transduction; neoplasm; neoplasms; metabolism; transforming growth factor beta; immunotherapy; pd-1; programmed death 1 ligand 1; tumor microenvironment; pd-l1; crosstalk; procedures; tgfΒ; humans; human; b7-h1 antigen; dual blockade therapy |
| Journal Title: | Expert Opinion on Investigational Drugs |
| Volume: | 31 |
| Issue: | 11 |
| ISSN: | 1354-3784 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2022-01-01 |
| Start Page: | 1187 |
| End Page: | 1202 |
| Language: | English |
| DOI: | 10.1080/13543784.2022.2152323 |
| PUBMED: | 36448335 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Review -- Export Date: 3 January 2023 -- Source: Scopus |
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