bims-tumime 2024-03-31 papers

Issue of 2024–03–31
four papers selected by
Alex Muir, University of Chicago

Cell Rep. 2024 Mar 23. pii: S2211-1247(24)00323-1. [Epub ahead of print]43(4): 113995

ATF4-SLC7A11-GSH axis mediates the acquisition of immunosuppressive properties by activated CD4+ T cells in low arginine condition.

Ziqi Zou, Qian Cheng, Jiajie Zhou, Chenyao Guo, Andreas V Hadjinicolaou, Mariolina Salio, Xinghua Liang, Cuiyu Yang, Yue Du, Weiran Yao, Dongrui Wang, Vincenzo Cerundolo, Qingqing Wang, Meng Xia.

The tumor microenvironment (TME) is restricted in metabolic nutrients including the semi-essential amino acid arginine. While complete arginine deprivation causes T cell dysfunction, it remains unclear how arginine levels fluctuate in the TME to shape T cell fates. Here, we find that the 20-μM low arginine condition, representing the levels found in the plasma of patients with cancers, confers Treg-like immunosuppressive capacities upon activated T cells. In vivo mouse tumor models and human single-cell RNA-sequencing datasets reveal positive correlations between low arginine condition and intratumoral Treg accumulation. Mechanistically, low arginine-activated T cells engage in metabolic and transcriptional reprogramming, using the ATF4-SLC7A11-GSH axis, to preserve their suppressive function. These findings improve our understanding of the role of arginine in human T cell biology with potential applications for immunotherapy strategies.

Keywords: CP: Immunology; SLC7A11; T cells; arginine; immunosuppression; tumor microenvironment

DOI: https://doi.org/10.1016/j.celrep.2024.113995

Cancer Lett. 2024 Mar 26. pii: S0304-3835(24)00230-1. [Epub ahead of print] 216837

The emerging role of lactate in tumor microenvironment and its clinical relevance.

Sihan Chen, Yining Xu, Wei Zhuo, Lu Zhang.

In recent years, the significant impact of lactate in the tumor microenvironment has been greatly documented. Acting not only as an energy substance in tumor metabolism, lactate is also an imperative signaling molecule. It plays key roles in metabolic remodeling, protein lactylation, immunosuppression, drug resistance, epigenetics and tumor metastasis, which has a tight relation with cancer patients' poor prognosis. This review illustrates the roles lactate plays in different aspects of tumor progression and drug resistance. From the comprehensive effects that lactate has on tumor metabolism and tumor immunity, the therapeutic targets related to it are expected to bring new hope for cancer therapy.

Keywords: Drug resistance; Lactic acid; Lactylation; Metabolic symbiosis; Tumor progression

DOI: https://doi.org/10.1016/j.canlet.2024.216837

Metabolites. 2024 Mar 19. pii: 171. [Epub ahead of print]14(3):

The Noncanonical Functions of Metabolites in Tumor Progression.

Siyang Wu, Yijun Qi, Weiwei Yang.

Metabolic reprogramming has emerged as a prominent hallmark of cancer, characterized by substantial alterations in nutrient uptake and intracellular metabolic pathways. Consequently, intracellular metabolite concentrations undergo significant changes which can contribute to tumorigenesis through diverse mechanisms. Beyond their classical roles in regulating metabolic pathway flux, metabolites exhibit noncanonical functions that play a crucial role in tumor progression. In this review, we delve into the nonclassical functions of metabolites in the context of tumor progression, with a particular focus on their capacity to modulate gene expression and cell signaling. Furthermore, we discuss the potential exploitation of these nonclassical functions in the enhancement of cancer therapy.

Keywords: metabolic reprogramming; metabolites; noncanonical functions of metabolites; tumor progressions

DOI: https://doi.org/10.3390/metabo14030171