Dendritic cells (DCs), as pivotal antigen-presenting cells (APCs), play crucial roles in initiating T cell-mediated antitumor immune responses, bridging innate and adaptive immunity while maintaining immune tolerance. With an in-depth understanding of DC biology and functions, numerous DC-targeted therapeutic approaches have been developed. An enhanced understanding of DC heterogeneity and DC cross-talk with other cells within the tumor microenvironment (TME), along with functional and metabolic remodeling mechanisms, may optimize DC-based cancer immunotherapies. This review focuses on the heterogeneity of the individual occurrence and function of DCs in tumors, elucidates the cross-talk between DCs and other cells in the TME, provides an in-depth understanding of the dysfunction and metabolic reprogramming of DCs in the TME, and summarizes existing DC-based anticancer therapies and novel therapeutic strategies, with the aim of providing new insight into the emerging role of DCs in future cancer immunotherapy.

BACKGROUND:MicroRNAs (miRNAs) are a class of small non-coding RNAs that are strongly involved in various types of carcinogenesis, including hepatocellular carcinoma (HCC). This study aimed to clarify whether miR-4417 promotes HCC growth by targeting ...

Background: Neuroendocrine tumors (NETs) are rare, which has resulted in a lack of published data on their epidemiology and clinical features. We therefore aimed to investigate the epidemiology, clinical features, treatments, and prognosis of patients with NETs.Methods: The clinicopathologic characteristics of 547 patients who were pathologically diagnosed with NETs were retrospectively analyzed, including age, sex, primary and metastatic sites, symptoms, pathology, treatment, and prognosis.Results: The 547 patients had a wide age range (9‐87 years), with a male to female ratio of 1:1.1. The primary tumor sites included 413 in the digestive system, 74 in the lung, 15 in the mediastinum, 8 in unknown sites, and 37 in other sites. Of the 413 patients with digestive system NETs, the pancreas, rectum, and stomach were the most common primary sites. Blood metastases were found in 84 patients at initial diagnosis, and the liver, bone, and lung were the most frequent sites of metastasis. Lymph node metastases were found in 82 patients at initial diagnosis. Surgery and chemotherapy were the most widely applied treatments. Statistical analysis showed that age <50 years, female sex, lower‐grade tumor, no distant metastasis, intestinal NET and surgery indicated a favorable prognosis.Conclusions: A difference between China and other countries is that small intestinal NETs are quite common in other countries but are rare in China. In China, the most common primary sites are the pancreas, rectum, and stomach. Furthermore, no unified treatments exist, though prognoses could be improved by using methods such as surgery, targeted therapies, and somatostatin analogs.Clinical Trial Registration: This study was not a clinical trial.

The 5-year survival rate of patients with hepatocellular cancer (HCC) was very low because of invasion and metastasis in the early stage. Biomarkers might help predict early occurrence of invasion and metastasis. Accumulating evidence has shown that deleted in liver cancer-1 (DLC1) may be considered as a metastasis suppressor gene in numerous solid and hematological cancers. However, its prognostic role and mechanisms that regulate and coordinate these activities remain poorly understood. With the method of immunohistochemistry, the expression of DLC-1 as well as Rho A, ROCK2, moesin had been characterized in 80 HCC tissues and adjacent noncancerous tissues. The correlation between their expression and their relationships with clinicopathological characteristics of HCC were also investigated. In addition, the prognostic value of DLC1 expression within the tumor tissues was assessed by Cox regression and Kaplan-Meier analysis. DLC1 expression was significantly lower in HCC tissues than in adjacent noncancerous tissues, and DLC-1 expression was found to be negatively correlated with tumor differentiation, TNM stage and lymph node metastasis. Furthermore, DLC-1 expression was found to inversely correlate with Rho A, ROCK2 and moesin which were all highly expressed in HCC tissues. Kaplan-Meier analysis showed that significantly longer 5-year survival rate was seen in HCC patients with higher DLC1 expression, compared to those with lower expression of DLC1. Multivariate Cox proportional hazard analyses revealed that DLC1 was an independent factor affecting the overall survival probability. DLC1 could be served as a tumor suppressor gene in the progression especially in the invasion and metastasis of HCC. DLC1 perhaps played its role by regulating the expression of Rho A, ROCK2 and moesin. Evaluation of the expression of DLC-1 might be a good prognostic marker for patients with HCC.

T cells expressing programmed cell death 1 (PD-1) in the peripheral blood (PB) of patients with tumors possess therapeutic potential; however, the immunosuppressive, PD-1–triggered signaling pathway and limited proliferative capacity of PD-1+ T cells present challenges to their therapeutic application. Here, we observed no discernible distinction between PD-1+ and PD-1− T cells in terms of clonal overlap. However, CD8+PD-1+ T cells from PB and tumor tissues exhibited tighter clustering based on clone size. Single-cell RNA sequencing analysis showed that PD-1+ T cells from PB highly expressed cytotoxicity-related genes and were enriched for T-cell activation–related pathways compared with PD-1− T cells from PB or tumor tissues. Consistent with this, PB-derived PD-1+ T cells exhibited strong cytotoxicity toward autologous tumor cells and tumor cell lines. To augment PD-1+ T-cell activity against solid tumors in vivo, we introduced a PD-1/CD28 fusion receptor combined with a CD19 chimeric antigen receptor into PD-1+ T cells, which were then expanded in vitro. The modified PD-1+ T cells exhibited superior proliferation and antitumor abilities in vitro. In addition, four patients with cancer were infused with autologous PD-1/CD28–CD19 chimeric antigen receptor PD-1+ T cells. None of these patients experienced severe side effects, and one patient with melanoma achieved a complete response that was maintained for 6.7 months. The three other patients had stable disease. Collectively, these results suggested that cell therapy with modified PB-derived PD-1+ T cells is both safe and effective, and it may constitute a promising treatment strategy for patients with cancer.

Background: Hepatocellular carcinoma (HCC) is one of the cancers of highest incidence and mortality worldwide. The proliferation and invasion of tumor cells are the main reason for poor prognosis after HCC surgery. Long non-coding RNA (lncRNA) has been shown to play a key role in the progression of HCC. LncRNA-CR594175 is one of the highly expressed lncRNAs in HCC tumors and their metastatic tumors that we have obtained by the High-throughput screening method. Methods: To elucidate the role of lncRNA-CR594175 in regulating the proliferation and invasion of human hepatoma cell line, HepG2, we operated through lncRNA-CR594175 silencing to inhibit the progression of HCC, either through in vitro or in vivo experiments. Results: We found that lncRNA-CR594175 was lower in adjacent non-cancerous tissues than in primary HCC, and was lower in primary HCC than in its metastasis. Silencing of lncRNA-CR594175 inhibited the proliferation and invasion of HepG2 cells and growth of subcutaneous tumors. The results revealed that lncRNA-CR594175, as a RNA sponge, broke the negative regulation of hsa-miR-142-3p on Catenin, beta-1 (CTNNB1), and once lncRNA-CR594175 was silenced, the hsa-miR142-3p regained its negative regulation on CTNNB1 which can promote HCC progression by activating the wnt pathway. Conclusions: Our present study demonstrated for the first time that lncRNA-CR594175 silencing suppressed proliferation and invasion of HCC cells in vivo and in vitro by restoring the negative regulation of hsa-miR-142-3p on CTNNB1, laying a solid theoretical base for using lncRNA-CR594175 as genetic target therapy for HCC and offering a reasonable explanation for inactivation of miRNA in different tumors or in the tumor at different stages.