Lipid metabolic features of T cells in the Tumor Microenvironment.

The tumor microenvironment (TME) is characterized by discrete changes in metabolic features of cancer and immune cells, with various implications. Cancer cells take up most of the available glucose to support their growth, thereby leaving immune cells with insufficient nutrients to expand. In the relative absence of glucose, T cells switch the metabolic program to lipid-based sources, which is pivotal to T-cell differentiation and activation in nutrient-stressed TME. Although consumption of lipids should provide an alternative energy source to starving T cells, a literature survey has revealed that it may not necessarily lead to antitumor responses. Different subtypes of T cells behave differently in various lipid overload states, which widely depends upon the kind of free fatty acids (FFA) engulfed. Key lipid metabolic genes provide cytotoxic T cells with necessary nutrients for proliferation in the absence of glucose, thereby favoring antitumor immunity, but the same genes cause immune evasion in Tmem and Treg. This review aims to detail the complexity of differential lipid metabolism in distinct subtypes of T cells that drive the antitumor or pro-tumor immunity in specific TME states. We have identified key drug targets related to lipid metabolic rewiring in TME.

KIF18b-dependent hypomethylation of PARPBP gene promoter enhances oxaliplatin resistance in colorectal cancer.

As the new platinum drug oxaliplatin has been widely used in clinical treatment of colorectal cancer (CRC), oxaliplatin resistance has become a burning problem. In this study, higher expression of PARP-1 binding protein (PARPBP) was detected in oxaliplatin-resistant CRC (OR-CRC) cells than in non-resistant cells. Further research showed that kinesin family member 18 b (KIF18b) induced the overexpression of PARPBP, sustaining oxaliplatin resistance in OR-CRC cells. Through exploring the PARPBP gene promoter, we found that SP1-recruited DNMT3b methylated PARPBP promoter to suppress transcription in CRC cells, and increased KIF18b attenuated the recruitment of DNMT3b to PARPBP promoter by directly interacting with SP1 in OR-CRC cells. Clinical analysis suggested a positive relationship between KIF18b and PARPBP in CRC tissues and indicated poor prognosis in CRC patients with high level of KIF18b or PARPBP. In summary, KIF18b-induced PARPBP contributes to the resistant phenotype of OR-CRC.