Dendritic cells (DCs) are antigen-presenting cells that play a crucial role in initiating immune responses by cross-presenting relevant antigens to initial T cells. The activation of DCs is a crucial step in inducing anti-tumor immunity. Upon recognition and uptake of tumor antigens, activated DCs present these antigens to naive T cells, thereby stimulating T cell-mediated immune responses and enhancing their ability to attack tumors. It is particularly noted that DCs are able to cross-present foreign antigens to major histocompatibility complex class I (MHC-I) molecules, prompting CD8⁺ T cells to proliferate and differentiate into cytotoxic T cells. In the malignant progression of hepatocellular carcinoma (HCC), the inactivation of DCs plays an important role, and the activation of DCs is particularly important in anti-HCC immunotherapy. In this review, we summarize the mechanisms of DCs activation in HCC, the involved regulatory factors and strategies to activate DCs in HCC immunotherapy. It provides a basis for the study of HCC immunotherapy through DCs activation.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is associated with high morbidity and mortality rates. The aims of this study were to investigate the immune-promoting action of nucleolar and spindle-associated protein 1 (NUSAP1) and identify an immunotherapy target for HCC. The Cancer Genome Atlas (TCGA) was used to analyze interaction molecules and immune correlation. The interaction between NUSAP1 and SHC binding and spindle associated 1 (SHCBP1) was examined. The role of the SHCBP1/Janus kinase 2/signal transducer and activator of transcription 3 (SHCBP1/JAK2/STAT3) pathway in this process was explored. After co-culture with HCC cell lines, the differentiation of peripheral blood mononuclear cells (PBMCs) into dendritic cells (DC) was evaluated by measuring the expression of surface factors CD1a and CD86. Pathological tissues from 50 patients with HCC were collected to validate the results of cell experiments. The expression levels of CD1a and CD86 in tissues were also determined. The results show that NUSAP1 interacted with SHCBP1 and was positively correlated with DC. In HCC cell lines, an interaction was observed between NUSAP1 and SHCBP1. It was verified that NUSAP1 inhibited the JAK2/STAT3 phosphorylation pathway by blocking SHCBP1. After co-culture, the levels of CD1a and CD86 in PBMC were elevated. In the clinical specimens, CD1a and CD86 expression levels were significantly higher in the high-NUSAP1 group versus the low-NUSAP1 group. In Summary, NUSAP1 enhanced immunity by inhibiting the SHCBP1/JAK2/STAT3 phosphorylation pathway and promoted DC generation and HCC apoptosis. NUSAP1 may be a target of immunotherapy for HCC.

Since neural invasion (NI) is a key factor leading to poor prognosis of patients with colorectal cancer (CRC), exploring its mechanism in CRC is an urgent challenge. In this study, lysine demethylase 3B (KDM3B), a differential protein for NI in CRC, was detected by TMT-seq of clinical CRC tissues (control vs. NI). Cut-tag and ATAC-seq of CRC cell line (control vs. sh-KDM3B) found that KDM3B promoted the expression of TrkA-encoding sequence NTRK1 in CRC, which was then verified through in vivo and in vitro experiments. The results demonstrated that overexpression of KDM3B in CRC could inhibit H3K9me2, which in turn contributed to the upregulation of TrkA, enabling binding of nerve growth factor (NGF) to it and ultimately inducing CRC NI. The present study reveals the intrinsic mechanism of NI in CRC, which lays a solid theoretical foundation for using KDM3B as a prognostic indicator and therapeutic target for CRC.

Background: Discovering new and effective drugs is a top priority for treating ovarian cancer, a gynecological tumor with a high mortality rate. As a major active ingredient isolated from Paris polyphylla , Polyphyllin H exhibits antitumor effect. However, its efficacy in ovarian cancer remains unknown. This study is designed to elucidate the antitumor activity and underlying mechanism of polyphyllin H in ovarian cancer. Materials and methods: Polyphyllin H was selected from 20 traditional Chinese medicine monomers based on its high anti-proliferative activity in CCK-8 assays performed on human ovarian cancer cell lines. The effects of polyphyllin H at different concentrations on cultured ovarian cancer cells were evaluated. Polyphyllin H was administered intragastrically to the cell line-derived xenograft (CDX) mice with ovarian cancer and the tumor inhibitory effects were assessed, and the potential anti-ovarian cancer mechanisms were predicted through protein sequencing. Subsequently, the therapeutic potential was further verified in patient-derived xenograft (PDX) mouse model. Results: The in vitro experiments demonstrated that polyphyllin H potently inhibited the proliferation, invasion, and migration of ovarian cancer cells while promoting cellular apoptosis. In vivo studies further confirmed that polyphyllin H significantly suppressed ovarian tumor growth, without inducing hepatic, renal and hematopoietic dysfunction, intestinal flora disturbance and major visceral histopathological change. Mechanistically, polyphyllin H upregulated cingulin (CGN) expression, blocking the RhoA/Rock2 signaling pathway to inhibit ovarian cancer malignant progression. Notably, polyphyllin H exerted promising antitumor efficacy in ovarian cancer PDX model, particularly demonstrating superior therapeutic effects against Her2-positive ovarian cancer. Conclusion: This study demonstrates that polyphyllin H inhibits the malignant progression of ovarian cancer via the CGN/RhoA/Rock2 pathway, without notable toxic and side effects. It provides a novel candidate drug for ovarian cancer therapy. Notably, the efficacy of polyphyllin H in ovarian cancer PDX models indicates its translational potential for clinical application.