Abstract
Although immunotherapy has achieved good results in various cancer types, a large proportion of patients are limited from the benefits. Hypoxia and metabolic reprogramming are the common and critical factors that impact immunotherapy response. Here, we present current research on the metabolism reprogramming induced by hypoxia on antitumor immunity and discuss the recent progression among preclinical and clinical trials exploring the therapeutic effects combining targeting hypoxia and metabolism with immunotherapy. By evaluating the little clinical translation of the combined therapy, we provide insight into “understanding and regulating cellular metabolic plasticity under the current tumor microenvironment (TME),” which is essential to explore the strategy for boosting immune responses by targeting the metabolism of tumor cells leading to harsh TMEs. Therefore, we highlight the potential value of advanced single-cell technology in revealing the metabolic heterogeneity and corresponding phenotype of each cell subtype in the current hypoxic lesion from the clinical patients, which can uncover potential metabolic targets and therapeutic windows to enhance immunotherapy.
Highlights
Since the Food and Drug Administration (FDA)-approved immune checkpoint blockade (ICB) in 2011, immunotherapy has achieved unprecedented advances in clinical treatment among various cancer types [1]
We recognize that the success of antitumor therapies is widely influenced by insufficient oxygen, metabolism reprogramming, and by-products induced by hypoxia in the local tumor microenvironment (TME); interpreting how these processes influence immune cell function could be applied in immunotherapy
Exploring which characteristics of the TME have the greatest impact on immune cells, blocking pathways leading to the current TME, will alleviate harsh TME and selectively affect the protumor cells demand those pathways and enhance the antitumor function of effector cells
Summary
Since the Food and Drug Administration (FDA)-approved immune checkpoint blockade (ICB) in 2011, immunotherapy has achieved unprecedented advances in clinical treatment among various cancer types [1]. It seems like regulating hypoxia-induced metabolism of tumor cells and immunosuppressive cells could improve the antitumor immune response and inhibit tumor growth.
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