The concept of immunoediting, a process whereby the immune system eliminates immunogenic cancer cell clones, allowing the remaining cells to progress and form a tumor, has evolved with growing appreciation of the importance of cancer ecology on tumor progression. As cancer cells grow and modify their environment, they create spatial and nutrient constraints that may affect not only immune cell function but also differentiation, tipping the balance between cytotoxic and regulatory immunity to facilitate tumor growth. Here, we review how immunometabolism may contribute to cancer escape from the immune system, as well as highlight an emerging role of gut microbiota, its effects on the immune system and on response to immunotherapy. We conclude with a discussion of how these pieces can be integrated to devise better combination therapies and highlight the role of computational approaches as a potential tool to aid in combination therapy design. Stem Cells 2019;37:1273-1280.
Keywords: Combination therapies; Gut microbiota; Homeostasis; Immunoediting; Immunometabolism.
©AlphaMed Press 2019.