As a significant public health problem with high morbidity and mortality worldwide, tumor is one of the major diseases endangering human life. Moreover, metastasis is the most important contributor to the death of tumor patients. Epithelial-mesenchymal transition (EMT) is an essential biological process in developing primary tumors to metastasis. It underlies tumor progression and metastasis by inducing a series of alterations in tumor cells that confer the ability to move and migrate. Tumor-associated macrophages (TAMs) are one of the primary infiltrating immune cells in the tumor microenvironment, and they play an indispensable role in the EMT process of tumor cells by interacting with tumor cells. With the increasing clarity of the relationship between TAMs and EMT and tumor metastasis, targeting TAMs and EMT processes is emerging as a promising target for developing new cancer therapies. Therefore, this paper reviews the recent research progress of tumor-associated macrophages in tumor epithelial-mesenchymal transition and briefly discusses the current anti-tumor therapies targeting TAMs and EMT processes.

Background: N⁷-methylguanosine (m7G), one of the most common post-transcriptional modifications, can be present in tRNA, mRNA, and miRNA to mediate the progression of various tumors. However, the possible role of m7G in gastric cancer (GC) is still unknown.Materials and Methods: In this study, SNVs (single nucleotide variations), CNVs (copy number variations), and methylation of m7G-related genes (m7GRGs) were analyzed. The relationship between them and the expression of m7GRGs and prognosis of GC patients was explored. Based on 13 prognostic-related m7GRGs, 567 GC samples were classified into three subtypes using the ConsensusClusterPlus package. we compared survival status, clinical traits, immune cell infiltration, immune checkpoints, tumor microenvironment (TME), tumor immune dysfunction and exclusion (TIDE), and potential biological pathways among the three subtypes. Then, patients were again grouped into different genetic subtypes based on the DEGs among the three subtypes. In addition, a prognostic m7GRG_Score was constructed using five risk genes applicable to patients of any age, gender and stage. We also assessed tumor mutational burden (TMB), microsatellite instability (MSI), cancer stem cell (CSC) index, sensitivity of antineoplastic drugs, efficacy of anti-PD-1 and anti-CTLA4 immunotherapy between high and low m7GRG_Score groups. Finally, we established a nomogram based on m7GRG_Score and tumor stage to enhance the clinical application of the model. miRNAs and lncRNAs that could regulate expression of risk genes were searched.Results: SNVs, CNVs, and methylation of m7GRGs were associated with m7GRGs expression. However, they did not significantly affect the survival of GC patients. Our results also confirmed that patients in subtypes B and C and low m7GRG_Score groups had longer survival time, better clinical stage, more immune cell infiltration, fewer immune escape and dysfunction compared to subtype A and high m7GRG_Score groups. A low m7GRG_score was featured with increased microsatellite instability-high (MSI-H), TMB, and efficacy of immunotherapy.Conclusion: The m7GRG_Score model may become a beneficial tool for predicting prognosis and guiding personalized treatment in GC patients. These findings will improve our knowledge of m7G in GC and provide new methods for more effective treatment strategies.

In recent years, numerous studies have demonstrated that the tumor immune microenvironment (TIME) is capable of regulating the growth of tumors, and tumor-infiltrating immune cells in the TIME can affect the prognosis and treatment responses of patients. Consequently, therapies targeting these immune cells have emerged as important antitumor treatments. As a crucial componet of the perioperative treatment of malignant tumors, neoadjuvant chemotherapy (NACT) can improve the surgical resection rate and prognosis of patients and is a suitable clinical model to evaluate the effect of chemotherapy on the TIME. To provide a rationale for developing valid combinational therapies, this review summarizes the impact of NACT on the TIME, the relationship between tumor-infiltrating immune cells and treatment responses of patients, and the prognostic value of these infiltrating immune cells.

Gastric cancer remains one of the most prevalent tumors worldwide and peritoneal metastasis is responsible for approximately 60% of death in advanced gastric cancer patients. However, the underlying mechanism of peritoneal metastasis is poorly understood. We have established organoids derived from malignant ascites (MA) of gastric cancer patients and noticed that MA supernatant could strongly increase the colony formation of organoids. Thus, we realized the interaction between exfoliated cancer cells (ECCs) and liquid tumor microenvironment contributes to peritoneal metastasis. Further, we designed a medium component control test which proved that exosomes derived from MA could not enhance the growth of organoids. Using Immunofluorescence and confocal imaging as well as dual-luciferase reporter assay, our data showed WNT signaling pathway was upregulated by high concentrations of WNT ligands (wnt3a and wnt5a), which was verified by ELISA. Besides, suppressing WNT signaling pathway diminished the growth promoting function of MA supernatant. This result implicated WNT signaling pathway as a potential therapeutic target for peritoneal metastasis of gastric cancer.