Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.01956
Keywords
immune checkpoint inhibitor; PD-1; PD-L1; anti-angiogenesis; tumor microenvironment; combination therapy
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Funding
- National Nature Science Foundation of China [81272619, 81572875]
- Natural Science Foundation of Hubei Province [2019CFB635]
- Health Commission of Hubei Province [WJ2019M194]
- CSCOHengrui Cancer Research Foundation [Y-HR2018-328]
- CSCO-BMS Cancer Immunotherapy Research Foundation [Y-BMS2019-003]
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Advances in cancer immunity have promoted a major breakthrough in the field of cancer therapy. This is mainly associated with the successful development of immune checkpoint inhibitors (ICIs) for multiple types of human tumors. Blockade with different ICIs, including programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, may activate the immune system of the host against malignant cells. However, only a subgroup of patients with cancer would benefit from immune checkpoint blockade. Some patients experience primary resistance to initial immunotherapy, and a majority eventually develop acquired resistance to ICIs. However, the mechanisms involved in the development of drug resistance to immune checkpoint blockade remain unclear. Recent studies supported that combination of ICIs and anti-angiogenic agents could be a promising therapeutic strategy for overcoming the low efficacy of ICIs. Moreover, through their direct anti-cancer effect by inhibiting tumor growth and metastasis, anti-angiogenic drugs reprogram the tumor milieu from an immunosuppressive to an immune permissive microenvironment. Activated immunity by immune checkpoint blockade also facilitates anti-angiogenesis by downregulating the expression of vascular endothelial growth factor and alleviating hypoxia condition. Many clinical trials showed an improved anti-cancer efficacy and prolonged survival following the addition of anti-angiogenic agents to ICIs. This review summarizes the current understanding and clinical development of combination therapy with immune checkpoint blockade and anti-angiogenic strategy.
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