Pancreatic cancer (PC) is an aggressive and fatal malignant tumor, and exosomes have been reported to be closely related to PC invasion and metastasis. Here we found that Exo70, a key subunit of the exocyst complex, promoted PC metastasis by regulating the secretion of tumor exosomes. Clinical sample studies showed that Exo70 was highly expressed in PC and negatively correlated with patients’ survival. Exo70 promoted PC cell lines’ invasion and migration. Interestingly, knockdown of Exo70, or using an Exo70 inhibitor (ES2) inhibited the secretion of tumor exosomes and increased the accumulation of cellular vesicles. Furthermore, Exo70 was found to accumulate in the exosomes, which then fused with neighboring PC cells and promoted their invasion. Moreover, Exo70 increased the expression of exosomal PD-L1, leading to the immune escape of PC cells. In vivo, knockdown of Exo70 or treatment with ES2 both decreased the tumor metastasis of PC cells in mice. This study provides new insight into the mechanism of invasion and metastasis in PC and identifies Exo70 as a potential prognostic factor and therapeutic target for PC.

Background: Claudin-18.2 (CLDN18.2) has emerged as a promising therapeutic target for gastric cancer due to its frequent and specific expression in malignant lesions. Dendritic cell (DC)-based vaccines represent a potent strategy for inducing antitumor immunity; however, their efficacy against solid tumors, such as gastric cancer, remains challenging. Methods: We developed a lentiviral vector encoding human CLDN18.2 (Lv-CLDN18.2) to generate antigen-loaded DC vaccines. In vitro, human monocyte-derived DCs were transduced and co-cultured with autologous T cells to induce cytotoxic T lymphocytes (CTLs). CTL function was assessed by flow cytometry, cytokine ELISA, and cytotoxicity assays against CLDN18.2-positive gastric cancer cells. In vivo, the therapeutic efficacy of the DC vaccine was evaluated in a syngeneic mouse model subcutaneously inoculated with MFC-CLDN18.2 cells. Results: We successfully produced high-titer Lv-CLDN18.2 and established stable CLDN18.2-positive gastric cancer cell lines. Lv-CLDN18.2-transduced DCs exhibited a mature phenotype with upregulated co-stimulatory (CD80/CD86) and antigen-presenting molecules (HLA-ABC/DR). These DCs potently stimulated CTLs, leading to a significantly higher proportion of activated CD8⁺CD25⁺ T cells, enhanced secretion of IFN-γ and TNF-α, and potent, specific lysis of CLDN18.2-positive target cells in vitro. In mouse models, vaccination with Lv-CLDN18.2-DCs significantly suppressed tumor growth, which was associated with robust CD8⁺ T cell infiltration, reduced tumor cell proliferation (Ki-67), and decreased CLDN18.2-positive tumor cells in vivo. Conclusions: Our study demonstrates that a CLDN18.2-targeting DC vaccine can effectively induce potent antigen-specific CTL responses and elicit significant antitumor immunity in a preclinical model. These findings provide a strong rationale for the clinical development of CLDN18.2-directed DC-based immunotherapy for gastric cancer.

Background/Objectives: Reducing corticosteroid exposure has become an important objective in the management of chemotherapy-induced nausea and vomiting (CINV), given the dose-related toxicity of dexamethasone (DEX). This prospective phase III randomized (LD-NEPA: low-dose dexamethasone plus netupitant/palonosetron) study evaluated whether a reduced dose of 5 mg DEX could maintain antiemetic efficacy when combined with NEPA in patients receiving highly or moderately emetogenic chemotherapy (HEC/MEC). Methods: Adult patients were randomly assigned (1:1) to receive NEPA with either 5 mg DEX (5D group) or 8 mg DEX (8D group). Among 186 randomized patients, 180 were included in the analysis (89 in the 5D group and 91 in the 8D group). The primary endpoint was the complete response rate (CRR; no emesis and no rescue medication use) during the 0–168 h period. Secondary endpoints included phase-specific CRR, total control rate (TCR), complete control rate (CCR), daily incidence of nausea and vomiting, and safety outcomes. Results: The overall CRR was 78.7% in the 5D group and 70.3% in the 8D group. The between-group difference was 8.4% (95% CI: −1.5% to 19.0%), demonstrating the reduced-dose regimen was non-inferior, with the lower bound exceeding the prespecified −15% margin. Consistent results were observed across secondary endpoints. Treatment-related adverse events were mostly grade 1–2 and occurred with broadly comparable frequencies between the two groups. Conclusions: A single lower dose of 5 mg DEX is noninferior to an 8 mg dose combined with NEPA for preventing 168 h nausea and vomiting of diverse HEC/MEC, offering comparable efficacy while reducing corticosteroid exposure.

Gastric cancer (GC) has a high global incidence and mortality rate