Tumor-associated macrophages (TAMs), essential components of the tumor immune microenvironment (TIME), undergo metabolic reprogramming as part of functional adaptation. Tumor cells modulate TAMs through multiple mechanisms, including metabolic cross-feeding, cytokine production, extracellular vesicles, tumor-derived proteins (such as GRP78) and pathogen-associated patterns (such as Lipopolysaccharide) signaling mediators. In turn, metabolic alterations in TAMs fine-tune TAM function via intricate signaling networks with outcomes that vary across cancer types. These functional and phenotypic shifts enable TAMs to influence malignant cells and other TIME components, such as T cells, NK cells, and fibroblasts, through the secretion of inflammatory factors and changes in surface marker expression. This process establishes an extensive network of interconnected cellular crosstalk. In this review the metabolic alterations-intracellular signaling-TAM biology axis is linked to cancer progression contributions and the implications for immunotherapy across diverse malignancies. Building on these insights, current preclinical and clinical studies with a focus on TAMs were surveyed and the advantages and challenges of TAM-targeted therapeutic strategies were systematically evaluated. We anticipate that these perspectives will spur further investigation into TAM-specific immune targets and accelerate the development of next-generation cancer immunotherapies.

Cell cycle dysregulation is one of the most important hallmarks of cancer. Bioinformatics studies have suggested that trigger transposable element-derived 1 (TIGD1) is expressed at higher levels in the tumor tissues from the clinical hepatocellular carcinoma (HCC) samples and may be related to the cell cycle. However, the underlying mechanism is unclear. To explore the specific mechanism of TIGD1 regulating the growth of hepatocellular carcinoma cells, this paper first analyzed the growth of HCC cell line Hep3B with TIGD1 knockdown by using shRNA plasmid. The results show that cell growth is inhibited. Then, cell cycle analysis by flow cytometry was used to investigate the effect of TIGD1 knockdown on cell cycle of HCC. The results show that the cell cycle progression of the Hep3B cell line is mainly blocked in the G2/M phase. Next, Immunoprecipitation (IP) experiments were used to verify the protein molecules with which TIGD1 might interact. And the results show that TIGD1 may be bound to Aurora kinase interacting protein 1 (AURKAIP1). Further, the Co-IP experiment confirmed the interaction between TIGD1 and AURKAIP1. AURKAIP1 is known to regulate the proteasomal degradation pathway of Aurora kinase A (AURKA), and AURKA is a mitotic regulatory protein that is closely associated with cell cycle progression. The paper further explored the effect of TIGD1 on AURKA protein levels, and the results show that TIGD1 knockdown obviously decreases the protein level of AURKA without affecting its mRNA level in Hep3B cells. In conclusion, TIGD 1 may affect cell cycle progression by regulating the post-transcriptional levels of AURKA in HCC cells, thus affecting the development of HCC.