About this Research Topic
Cancer immunotherapy has been gradually recognized as a priority treatment in clinic. Promising immunotherapy strategies including cancer vaccine, immune check point blockade and adoptive cell therapy aim to increase the amount of functional cytotoxic CD8+ T cells by activating the host immune system or directly infusing these immune cells into patients. However, durable tumor control and regression are not observed for most patients in clinic. Increasing evidences show that tumor and stromal cells will aggressively consume most nutrients and oxygen to create a very harsh milieu characterized as acidosis, hypoxia, nutrient deprivation and full of harmful metabolites to CD8+ T cell. This disadvantage in metabolic competition and immunosuppressive milieu will result in metabolic unfitness for CD8+ T cells, finally driving them exhaustion and dysfunction. Thus, how to improve CD8+ T cells metabolic fitness is crucial to restore their effector function for durable cancer immunotherapy.
Metabolic intervention in tumor microenvironment has been considered as an innovative therapeutic approach to potentiate anti-tumor immunity. However, most metabolic modulators are small molecules and can’t specifically modulate the targets. For example, glycolysis inhibitors are adopted to inhibit the glycolysis of highly glycolytic tumor cells to alleviate the immunosuppressive microenvironment. However, activated CD8+ T cells also need glycolysis to fuel effector function. This random and uncontrollable metabolism inhibition may strengthen immunosuppression instead of relieving it. Additionally, distinct metabolic features and requirements exist in different T cell subpopulations along with metabolic reprogramming during anti-tumor immunity. Effector T cells prefer to use glycolysis as main metabolic pathway while OXPHOS is predominant in memory T cells. Thus specifically modulating the metabolism of different T cell subpopulations to keep their metabolic fitness is a big challenge. In recent years, many functional biomaterials have been developed to make micro/nanoparticles to achieve drug targeted delivery at tissue, cellular and even organelle level, which will promote the targeting metabolic intervention therapy. Moreover, functional materials can also be designed to form hydrogel or implant to modulate the tumor metabolic environment to potentiate the cancer immunotherapy.
In this Research Topic, we are trying to better understand the metabolic modulation in tumor microenvironment and find feasible solutions to achieve specific metabolic interventions based on functional materials or other promising strategies to improve metabolic fitness of T cells and potentiate cancer therapy. We encourage authors to submit Original Research, Review, mini-Review and Perspective articles, in the following themes, but not limited to:
Investigation of metabolism modulation and anti-tumor immunity
• Design and discovery of specific and novel metabolic modulators
• Targeting delivery of metabolic modulators for specific metabolic intervention
• Functional materials for tumor metabolic environment modulation
• Metabolic intervention and cancer therapy
Keywords: metabolic intervention, antitumor immunity, targeting delivery, functional materials, cancer therapy
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