Journal
JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Volume 40, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s13046-020-01820-7
Keywords
Cancer immunotherapy; Hypoxia; Tumor microenvironment; Hypoxia-inducible factor; Immune suppression; Resistance; Combination approaches
Categories
Funding
- National Natural Science Foundation of China [81570344]
- National Key R&D Program of China [2017YFC0112100]
- Education Department Foundation of Jilin Province [JJKH20201036KJ]
- Health and Family Planning Commission of Jilin Province Foundations [2016Q034, 2017 J11]
- Norman Bethune Program of Jilin University [2015225, 2015203]
- Fundamental Research Funds for the Central Universities of Jilin University
- Jilin Provincial Science and Technology Foundations [20180414039GH, 20190201200JC]
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Hypoxic tumor microenvironment (TME) may be a major barrier limiting the efficacy of immunotherapy, through inducing immune suppression and resistance. Targeting hypoxia could enhance the efficacy of immunotherapy and provide a promising combinational therapeutic strategy.
With the success of immune checkpoint inhibitors (ICIs), significant progress has been made in the field of cancer immunotherapy. Despite the long-lasting outcomes in responders, the majority of patients with cancer still do not benefit from this revolutionary therapy. Increasing evidence suggests that one of the major barriers limiting the efficacy of immunotherapy seems to coalesce with the hypoxic tumor microenvironment (TME), which is an intrinsic property of all solid tumors. In addition to its impact on shaping tumor invasion and metastasis, the hypoxic TME plays an essential role in inducing immune suppression and resistance though fostering diverse changes in stromal cell biology. Therefore, targeting hypoxia may provide a means to enhance the efficacy of immunotherapy. In this review, the potential impact of hypoxia within the TME, in terms of key immune cell populations, and the contribution to immune suppression are discussed. In addition, we outline how hypoxia can be manipulated to tailor the immune response and provide a promising combinational therapeutic strategy to improve immunotherapy.
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