Impact of Diets on Response to Immune Checkpoint Inhibitors (ICIs) Therapy against Tumors

Abstract

Immunotherapy has revolutionized the established therapeutics against tumors. As the major immunotherapy approach, immune checkpoint inhibitors (ICIs) achieved remarkable success in the treatment of malignancies. However, the clinical gains are far from universal and durable, because of the primary and secondary resistance of tumors to the therapy, or side effects induced by ICIs. There is an urgent need to find safe combinatorial strategies that enhance the response of ICIs for tumor treatment. Diets have an excellent safety profile and have been shown to play pleiotropic roles in tumor prevention, growth, invasion, and metastasis. Accumulating evidence suggests that dietary regimens bolster not only the tolerability but also the efficacy of tumor immunotherapy. In this review, we discussed the mechanisms by which tumor cells evade immune surveillance, focusing on describing the intrinsic and extrinsic mechanisms of resistance to ICIs. We also summarized the impacts of different diets and/or nutrients on the response to ICIs therapy. Combinatory treatments of ICIs therapy with optimized diet regimens own great potential to enhance the efficacy and durable response of ICIs against tumors, which should be routinely considered in clinical settings.

Keywords: diet; immune checkpoint inhibitor; resistance; tumor.

Figure 1

Immune evasion by tumors and effects of dietary factors on immune checkpoint inhibitors (ICIs) therapy. In the priming phase, T cells are activated by antigen-presenting cells (APCs) when T cell receptor (TCR) binds to the antigen displayed in the major histocompatibility complex (MHC) on APCs, e.g., dendritic cells (DCs), in concert with CD28:B7-mediated co-stimulation. In the case of a strong TCR stimulus, CTLA-4 expression is upregulated and competes with CD28 for binding B7 molecules. High levels of CTLA-4:B7 binding limit the survival of T cells and protect tumor cells from T cell attack. In the effector phase, prolonged tumor antigen stimuli cause an upregulation of PD-1 which binds to PD-L1 expressed by tumor cells. PD-1:PD-L1 binding leads to the exhaustion of T cells, which results in immune evasion by tumors. In addition, there are several types of cells, including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), tumor-associated macrophage (TAMs), and cancer-associated fibroblast (CAFs), which can inhibit the anti-tumor T-cell response via secreting various molecules. Immune checkpoint inhibitors (ICIs), e.g., anti-CTLA-4 and PD-1/PD-L1 antibodies, can reactivate the immune response of T cells to tumors. Emerging evidence suggests that certain dietary patterns and vitamins can synergistically enhance the efficacy of ICIs therapy by affecting the expression of immune checkpoint proteins.