Pemetrexed plus dendritic cells as third-line therapy for metastatic esophageal squamous cell carcinoma

Abstract

This study was conducted to evaluate the toxicity and efficacy of pemetrexed plus dendritic cells (DCs) when administered as third-line treatment for metastatic esophageal squamous cell carcinoma (ESCC). All patients in the study group had previously failed first-line treatment with 5-fluorouracil and cisplatin-based regimens, as well as second-line treatment with taxane-based regimens. A total of 31 patients were treated with pemetrexed (500 mg/m2) plus DCs on day 1, every 3 weeks. DCs were given for one cycle of 21 days. Thirty patients were evaluated for their response. No patient had a complete response, three patients (10.0%) had a partial response, ten patients (33.3%) had stable disease, and 17 patients (56.7%) had progressive disease. The overall response rate was 10.0%. The median progression-free survival (PFS) time was 2.9 months (95% CI, 2.7–3.2), and the median overall survival (OS) time was 7.1 months (95% CI, 6.4–7.9). The median PFS and OS times among patients with high and low levels of miR-143 expression in their blood serum were significantly different: median PFS times =3.2 months (95% CI, 2.9–3.4) and 2.7 months (95% CI, 2.4–3.0), respectively (P=0.017), and median OS times =7.8 months (95% CI, 6.8–8.9) and 6.3 months (95% CI, 5.3–7.3), respectively (P=0.036). No patient experienced Grade 4 toxicity. Combined third-line treatment with pemetrexed and DCs was marginally effective and well tolerated in patients with advanced ESCC. Serum miR-143 levels are a potential biomarker for predicting the efficacy of pemetrexed plus DCs in the treatment of ESCC.

Prognostic Value of MicroRNAs in Esophageal Carcinoma: A Meta-Analysis

“…The forest plots, Begg’s funnel plots, and sensitivity analyses are shown in Supplementary Figures 1 – 8 according to the logic sequencing of miRNA names. For the included 96 studies, 52 were excluded because the frequency of them evaluating prognostic value of miRNA was equal to 1 3 , 4 , 16 , 18 – 23 , 26 , 30 , 31 , 39 – 46 , 48 , 53 , 54 , 56 , 60 , 61 , 64 – 74 , 77 – 86 , 92 – 96 . In addition, although one article reported OS results about miR-193a-5p, it was excluded because it had non-dichotomous miRNA expression value 105 .…”

Esophageal cancer practice guidelines 2022 edited by the Japan esophageal society: part 1

“…Although the results of intervention studies of EGFR inhibitors/monotherapies/combination chemotherapies have been reported, there is no clear evidence to indicate whether third-line therapy might be effective for prolonging the survival [150,[157][158][159][160][161]. In addition, the safety and efficacy of anti-PD-1 antibody therapy have not yet been reported.…”

Innovative prognostic modeling in ESCC: leveraging scRNA-seq and bulk-RNA for dendritic cell heterogeneity analysis

“…Not only do they capture and present tumor antigens, but they also activate and modulate immune responses, impacting the mechanisms of tumor immune surveillance and escape ( 9 ). Previous studies have indicated that a combination therapy of pemetrexed and DCs as a third-line treatment for ESCC can significantly improve prognosis and is well-tolerated ( 10 ). Furthermore, in ESCC patients with regions rich in tertiary lymphoid structures, there is an increased infiltration of CD8+ T cells and DCs, which is associated with stronger anti-tumor immune activity ( 11 ).Specifically, conventional dendritic cells (cDCs) play a key role in cross-presenting tumor antigens and activating cytotoxic T cells; tolerogenic dendritic cells (tDCs) can modulate immune responses by inducing immune tolerance or generating regulatory T cells, thereby preventing overactive immune reactions ( 12 ); plasmacytoid dendritic cells (pDCs), primarily known for their role in antiviral responses, have an unclear role in the TME, possibly involving the modulation of the immune status of the TME ( 13 ).…”