Metabolic reprogramming in the tumour microenvironment: a hallmark shared by cancer cells and T lymphocytes.

Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and up-regulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system. Immune checkpoint blockade provides an example of how metabolism can be differentially impacted to impair cancer cells but support T cells. Implications for research with metabolic inhibitors are discussed.

Allison KE ，Coomber BL ，Bridle BW 《-》

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 《-》

Immunological Effects of Conventional Chemotherapy and Targeted Anticancer Agents.

The tremendous clinical success of checkpoint blockers illustrates the potential of reestablishing latent immunosurveillance for cancer therapy. Although largely neglected in the clinical practice, accumulating evidence indicates that the efficacy of conventional and targeted anticancer agents does not only involve direct cytostatic/cytotoxic effects, but also relies on the (re)activation of tumor-targeting immune responses. Chemotherapy can promote such responses by increasing the immunogenicity of malignant cells, or by inhibiting immunosuppressive circuitries that are established by developing neoplasms. These immunological "side" effects of chemotherapy are desirable, and their in-depth comprehension will facilitate the design of novel combinatorial regimens with improved clinical efficacy.

Galluzzi L ，Buqué A ，Kepp O ，Zitvogel L ，Kroemer G ... -  《-》

Treg programming and therapeutic reprogramming in cancer.

Overcoming the immunosuppressive tumour microenvironment is the major challenge impeding cancer immunotherapy today. Regulatory T-cells (Tregs) are prevalent in nearly all cancers and, as immunosuppressive regulators of immune responses, they are the principal opponents of cancer immunotherapy. However, disabling Tregs systemically causes severe autoimmune toxicity, hastening the need for more selective methods to target intratumoural Tregs. In this review, we discuss a burgeoning new modality to specifically target tumour-infiltrating Tregs (TI-Tregs) by reprogramming their functionality from immunosuppressive to immune stimulatory within tumours. As the basis for therapeutic selectivity of TI-Tregs, we will focus on the defining features of Tregs within cancer: their highly activated state controlled by the engagement of key surface receptors, their distinct metabolic programme, and their unique transcriptional programme. By identifying proteins and pathways that distinguish TI-Tregs from other Tregs in the body, as well as from the beneficial antitumour effector T-cells within tumours, we highlight mechanisms to selectively reprogramme TI-Tregs for the treatment of cancer.

Moreno Ayala MA ，Li Z ，DuPage M 《-》

Editorial: T Cell Exhaustion.

Bonorino C ，Mognol G 《Frontiers in Immunology》