bims-mecami 2024-11-10 papers

Issue of 2024–11–10
four papers selected by
Oltea Sampetrean, Keio University

Cold Spring Harb Perspect Med. 2024 Nov 05. pii: a041814. [Epub ahead of print]

Cancer Metabolism: Historical Landmarks, New Concepts, and Opportunities.

Navdeep S Chandel, Karen H Vousden, Ralph J DeBerardinis.

Cancer cells undergo changes in metabolism that distinguish them from non-malignant tissue. These may provide a growth advantage by promoting oncogenic signaling and redirecting intermediates to anabolic pathways that provide building blocks for new cellular components. Cancer metabolism is far from uniform, however, and recent work has shed light on its heterogenity within and between tumors. This work is also revealing how cancer metabolism adapts to the tumor microenvironment, as well as ways in which we may capitalize on metabolic changes in cancer cells to create new therapies.

DOI: https://doi.org/10.1101/cshperspect.a041814

Metab Eng. 2024 Oct 25. pii: S1096-7176(24)00137-X. [Epub ahead of print]

Applying metabolic control strategies to engineered T cell cancer therapies.

Andrea C Fox, John Blazeck.

Chimeric antigen receptor (CAR) T cells are an engineered immunotherapy that express synthetic receptors to recognize and kill cancer cells. Despite their success in treating hematologic cancers, CAR T cells have limited efficacy against solid tumors, in part due to the altered immunometabolic profile within the tumor environment, which hinders T cell proliferation, infiltration, and anti-tumor activity. For instance, CAR T cells must compete for essential nutrients within tumors, while resisting the impacts of immunosuppressive metabolic byproducts. In this review, we will describe the altered metabolic features within solid tumors that contribute to immunosuppression of CAR T cells. We'll discuss how overexpression of key metabolic enzymes can enhance the ability of CAR T cells to resist corresponding tumoral metabolic changes or even revert the metabolic profile of a tumor to a less inhibitory state. In addition, metabolic remodeling is intrinsically linked to T cell activity, differentiation, and function, such that metabolic engineering strategies can also promote establishment of more or less efficacious CAR T cell phenotypes. Overall, we will show how applying metabolic engineering strategies holds significant promise to improve CAR T cells for the treatment of solid tumors.

Keywords: CAR T cell therapies; Cellular engineering; Immunotherapy; Metabolic engineering; Tumor microenvironment

DOI: https://doi.org/10.1016/j.ymben.2024.10.009

Curr Opin Biotechnol. 2023 Oct 27. pii: S0958-1669(23)00122-2. [Epub ahead of print]84 103012

Autophagy as a critical driver of metabolic adaptation, therapeutic resistance, and immune evasion of cancer.

Keisuke Yamamoto, Dosuke Iwadate, Eri Naito, Keisuke Tateishi, Mitsuhiro Fujishiro.

Autophagy is a well-conserved intracellular degradation pathway. Besides its physiological role in normal cells, autophagy is activated in various cancer types and protects cancer cells from stresses such as nutrient deprivation, therapeutic insults, and antitumor immunity. Autophagy in cancer cells as well as normal cells in the host supports tumor metabolism, allowing for tumor growth under a nutrient-limited tumor microenvironment. Autophagy also protects cancer cells from treatments such as radiation therapy, cytotoxic chemotherapy, and targeted therapy. Though the roles of autophagy in antitumor immunity are complex and highly context-dependent, accumulating evidence now supports the role of autophagy in mediating immunotherapy resistance. Based on these preclinical findings, multiple clinical trials are currently ongoing to test the therapeutic efficacy of autophagy inhibition in cancer. Here, we review recent findings on the tumor-promoting roles of autophagy in cancer and discuss advances in therapeutic approaches that target autophagy in cancer.

DOI: https://doi.org/10.1016/j.copbio.2023.103012

Int Immunopharmacol. 2024 Nov 01. pii: S1567-5769(24)02061-7. [Epub ahead of print]143(Pt 3): 113539

Ferroptosis in Cancer: A new perspective on T cells.

Yuping Lai, Chunxia Huang, Jiaqiang Wu, Kangping Yang, Liang Yang.

T cells occupy a pivotal position in the immune response against cancer by recognizing and eliminating cancer cells. However, the tumor microenvironment often suppresses the function of T cells, leading to immune evasion and cancer progression. Recent research has unveiled novel connections among T cells, ferroptosis, and cancer. Ferroptosis is a type of regulated cell death that relies iron and reactive oxygen species and is distinguished by the proliferation of lipid peroxides. Emerging scientific findings underscore the potential of ferroptosis to modulate the function and survival of T cells in the tumor microenvironment. Moreover, T cells or immunotherapy can also affect cancer by modulating ferroptosis in cancer cells. This review delved into the intricate crosstalk between T cells and ferroptosis in the context of cancer, highlighting the molecular mechanisms involved. We also explored the therapeutic potential of targeting ferroptosis to enhance the anticancer immune response mediated by T cells. Understanding the interplay among T cells, ferroptosis, and cancer may provide new insights into developing innovative cancer immunotherapies.

Keywords: Cancer; Ferroptosis; Immunotherapy; T cells

DOI: https://doi.org/10.1016/j.intimp.2024.113539