Metabolic reprograming of anti-tumor immunity.

Immunotherapies designed to trigger T cell destruction of tumor cells can result in sustained and complete responses in patients whose cancers were resistant to available treatment options. Evidence suggests that powering the T cell response - how T cells generate energy - plays an important role in their effectiveness. Furthermore the metabolism of T cells can be modulated to improve their anti-cancer activities. In this review, we will discuss the key metabolic properties of anti-cancer T cells, along with potential strategies to enhance immunotherapy through the modulation of T cell metabolism.

Sukumar M ，Kishton RJ ，Restifo NP 《-》

Metabolic Barriers to T Cell Function in Tumors.

The metabolic programs that drive T cell functions are exquisitely sensitive to cell intrinsic and extrinsic factors, allowing T cells to respond in a fine-tuned manner to a variety of immune challenges and conditions. However, many of the factors essential for effector T cell function are perturbed in the tumor microenvironment, where oncogenic mutations drive unrestrained cancer cell growth that leads to excess nutrient consumption, excess waste excretion, and insufficient oxygen delivery. This imposes metabolic constraints on infiltrating cells that result in dysfunction and loss of potential antitumor activity in both naturally occurring as well as tailored T cells introduced as part of immunotherapy. In this review, we highlight the metabolic properties that characterize tumor-infiltrating T cells, the barriers within the metabolic landscape of the tumor microenvironment, and the opportunities and challenges they present in development of new cancer therapeutics.

Sugiura A ，Rathmell JC 《-》

Antitumor T-cell Reconditioning: Improving Metabolic Fitness for Optimal Cancer Immunotherapy.

With the rapid rise of immunotherapy for cancer treatment, attention has focused on gaining a better understanding of T-cell biology in the tumor microenvironment. Elucidating the factors underlying changes in their function will allow for the development of new therapeutic strategies that could expand the patient population benefiting from immunotherapy, as well as circumvent therapy resistance. Cancers go beyond avoiding immune recognition and inducing T-cell dysfunction through coinhibitory molecules. Recent work has demonstrated that the tumor microenvironment elicits metabolic changes in T cells that dampen their ability to respond and that manipulating these metabolic changes can strengthen an antitumor immune response. Here we review the metabolic status of various types of T cells, the energetic state of the tumor microenvironment, and proposed modalities for improvement of immunotherapy through metabolic remodeling. Clin Cancer Res; 24(11); 2473-81. ©2018 AACR.

Rivadeneira DB ，Delgoffe GM 《-》

Fundamentals of T Cell Metabolism and Strategies to Enhance Cancer Immunotherapy.

Emerging reports show that metabolic pathways can be targeted to enhance T cell-mediated immunity to tumors. Yet, tumors consume key metabolites in the host to survive, thus robbing T cells of these nutrients to function and thrive. T cells are often deprived of basic building blocks for energy in the tumor, including glucose and amino acids needed to proliferate or produce cytotoxic molecules against tumors. Immunosuppressive molecules in the host further compromise the lytic capacity of T cells. Moreover, checkpoint receptors inhibit T cell responses by impairing their bioenergetic potential within tumors. In this review, we discuss the fundamental metabolic pathways involved in T cell activation, differentiation and response against tumors. We then address ways to target metabolic pathways to improve the next generation of immunotherapies for cancer patients.

Rangel Rivera GO ，Knochelmann HM ，Dwyer CJ ，Smith AS ，Wyatt MM ，Rivera-Reyes AM ，Thaxton JE ，Paulos CM ... -  《Frontiers in Immunology》

T-cell immunometabolism against cancer.

T cells play critical roles in host defenses against cancer. External signals prompt activation of naïve T cells, triggering modulation of their immune functions. Emerging evidence reveals that distinct metabolic changes impact the immune functions of naïve and effector T cells, including CD4+ and CD8+ T cells. Since T cells appear to be key players in tumor progression, it is important to elucidate whether and how T-cell metabolic reprogramming might alter their impact on cancer progression. Here we briefly review the available knowledge regarding T cells in relation to cancer, focusing on the metabolic reprogramming of T cells and how this influences tumor progression. Emerging insights in this field are improving our understanding of the functional role of T-cell metabolic reprogramming in cancer. Further research could provide a critical foundation for new treatments targeting cancer metabolism.

Jiang S ，Yan W 《-》