Metabolic reprogramming of immune cells within the tumor microenvironment (TME) plays a pivotal role in shaping tumor progression and responses to therapy. The intricate interplay between tumor cells and immune cells within this ecosystem influences their metabolic landscapes, thereby modulating the immune evasion tactics employed by tumors and the efficacy of immunotherapeutic interventions. This review delves into the metabolic reprogramming that occurs in tumor cells and a spectrum of immune cells, including T cells, macrophages, dendritic cells, and myeloid-derived suppressor cells (MDSCs), within the TME. The metabolic shifts in these cell types span alterations in glucose, lipid, and amino acid metabolism. Such metabolic reconfigurations can profoundly influence immune cell function and the mechanisms by which tumors evade immune surveillance. Gaining a comprehensive understanding of the metabolic reprogramming of immune cells in the TME is essential for devising novel cancer therapeutic strategies. By targeting the metabolic states of immune cells, it is possible to augment their anti-tumor activities, presenting new opportunities for immunotherapeutic approaches. These strategies hold promise for enhancing treatment outcomes and circumventing the emergence of drug resistance.

Background: The tumor microenvironment (TME) plays a crucial role in the progression of lung adenocarcinoma (LUAD). However, understanding its dynamic immune and stromal modulation remains a complex challenge. Methods: We utilized the ESTIMATE algorithm to evaluate the immune and stromal components of the LUAD TME from the TCGA database. Correlations between these components and clinical characteristics and patient prognosis were analyzed. Toll-like receptor 7 (TLR7) was identified as a key prognostic biomarker through PPI network and COX regression analysis. Validation of TLR7 expression was conducted using GEO data, qPCR, WB, and IHC. A prognostic model was developed using a nomogram, incorporating TLR7 expression. Enrichment analysis, the Tumor Immune Estimation Resource database, and single-sample gene set enrichment analysis were used to explore TLR7’s potential function. The response of the TLR7 subgroup to immunotherapy and drug sensitivity was observed. Results: We found significant associations between the immune and stromal components of LUAD TME and clinical features and prognosis. Specifically, TLR7 was identified as a prognostic biomarker, where lower expression in tumor tissues was linked to worse outcomes. This finding was further confirmed by comparing TLR7 expression in LUAD cells to normal bronchial epithelial cells, revealing lower expression in the tumor cells. Incorporating TLR7 into a nomogram prognostic model resulted in a good predictor of patient survival. Additionally, TLR7 was associated with immune function and positively correlated with various immune cells. Importantly, patients with high TLR7 expression were more likely to benefit from anti-PD-1 checkpoint blockade therapy. We also identified four treatment candidates for patients with high TLR7 expression. Conclusion: TLR7 is a powerful clinical feature that predicts patient prognosis, immunotherapeutic response, and drug candidates, providing additional insights for the treatment of LUAD.

RNA-binding proteins (RBPs), particularly IGF2BP3, play critical but underexplored roles in lung adenocarcinoma (LUAD). This study investigated IGF2BP3′s clinical and functional significance using single-cell/RNA sequencing, validated by qPCR, Western blot, and immunohistochemistry. The results show IGF2BP3 was significantly upregulated in LUAD tissues and associated with advanced-stage, larger tumors, lymph node metastasis, and poor prognosis. A prognostic nomogram confirmed its independent predictive value. Functionally, IGF2BP3 knockdown suppressed proliferation, and induced G2/M arrest and apoptosis. GSEA linked high IGF2BP3 to cell cycle activation and low expression to metabolic pathways. Notably, high IGF2BP3 correlated with immune evasion markers (downregulated CD4+ effector T cells, upregulated Th2 cells), while TIDE analysis suggested a better immunotherapy response in low-expressing patients. Drug screening identified BI-2536 as a potential therapy for low-IGF2BP3 cases, supported by strong molecular docking affinity (−7.55 kcal/mol). These findings establish IGF2BP3 as a key driver of LUAD progression and a promising target for immunotherapy and precision medicine.

Background: Breast cancer remains a major global health threat to women. While current therapies exist, their limitations necessitate novel strategies. Melatonin, an endogenous circadian regulator, has shown anti-tumor potential, but its mechanisms from a circadian perspective require further exploration. Methods: The anti-tumor effects of melatonin were evaluated through cell proliferation, colony formation, and apoptosis assays. Through data analysis and experimental verification at the RNA and protein levels, the regulatory effect of it on the core clock gene BMAL1 was studied. The role of BMAL1 in mediating melatonin’s suppression of glucose metabolism was assessed by measuring glucose uptake and lactate production. Downstream effector molecules of BMAL1 were identified through molecular interaction and transcriptional regulation analyses. Results: Melatonin significantly inhibited breast cancer cell proliferation and colony formation and induced apoptosis. Mechanistically, it upregulates the core clock gene BMAL1, which suppresses glucose metabolism. ALDH3A1 was identified as a key downstream target of BMAL1, defining a novel “melatonin-BMAL1-ALDH3A1” axis. In vivo studies confirmed that this axis effectively inhibits tumor growth without apparent toxicity, and SR8278 also shows a synergistic effect when used in combination with melatonin. Conclusions: Our findings elucidate the role of the “melatonin-BMAL1-ALDH3A1” axis in combating breast cancer, offering a new direction for treatment and laying the groundwork for developing precision chronotherapy-based combination regimens.

Radiotherapy is the standard radical therapy for locally advanced cervical cancer, with approximately 80% of patients receiving radiation treatment. Nevertheless, intrinsic or acquired radioresistance reduces therapeutic efficacy. Previous studies have confirmed that mRNA methylation modification, metabolic reprogramming and redox homeostasis are involved in the regulation of radioresistance; however, the specific molecular mechanism underlying radioresistance in cervical cancer remains unclear. We integrated transcriptomic–metabolomic profiling, cell-biological experiments, radiobiological assays, RIP, molecular rescue experiments, xenograft tumor models and clinical specimens to dissect this regulatory axis. We identified IGF2BP2 as a key molecule governing radioresistance in cervical cancer. IGF2BP2 binds to the m6A-modified sites on PHGDH mRNA to maintain its stability and subsequently potentiates serine metabolism. Excessive serine metabolism elevates intracellular GSH and SAM levels, sustains cellular antioxidant homeostasis and confers cellular radioresistance. Data from animal models and clinical specimens further validated this regulatory axis. This study uncovers the m6A-IGF2BP2-PHGDH–serine metabolism–antioxidant regulatory axis, providing promising prognostic biomarkers and a radiosensitizing strategy combining a serine-restricted diet with radiotherapy for cervical cancer.

Cervical cancer remains one of the major gynecological malignancies worldwide, with tumor immune evasion playing a critical role in disease progression. Although accumulating evidence has implicated BAP31 in tumor progression and immune regulation, its role in immune evasion in cervical cancer remains poorly understood. In this study, we found that BAP31 was significantly upregulated in cervical cancer tissues and that elevated BAP31 expression was associated with poor patient prognosis. Functional assays demonstrated that BAP31 silencing restored the immune activity of dendritic cells. Mechanistically, BAP31 was found to regulate TGF-β at the post-transcriptional level and to facilitate its transport from the endoplasmic reticulum to the Golgi apparatus through an interaction involving the Asn-381 residue, thereby affecting its intracellular maturation and extracellular secretion. Additional functional analyses showed that exogenous TGF-β impaired dendritic cell maturation and migration while enhancing phagocytic activity. Collectively, these findings indicate that BAP31 regulation of TGF-β contributes to dendritic cell dysfunction and the establishment of an immunosuppressive microenvironment in cervical cancer.