Prognostic significance of NY-ESO-1 antigen and PIGR expression in esophageal tumors of CHP-NY-ESO-1-vaccinated patients as adjuvant therapy.

The aim of this study was to determine the efficacy and the biomarkers of the CHP-NY-ESO-1 vaccine complexed with full-length NY-ESO-1 protein and a cholesteryl pullulan (CHP) in patients with esophageal squamous cell carcinoma (ESCC) after surgery. We conducted a randomized phase II trial. Fifty-four patients with NY-ESO-1-expressing ESCC who underwent radical surgery following cisplatin/5-fluorouracil-based neoadjuvant chemotherapy were assigned to receive either CHP-NY-ESO-1 vaccination or observation as control. Six doses of CHP-NY-ESO-1 were administered subcutaneously once every two weeks, followed by nine more doses once every four weeks. The endpoints were disease-free survival (DFS) and safety. Exploratory analysis of tumor tissues using gene-expression profiles was also performed to seek the biomarker. As there were no serious adverse events in 27 vaccinated patients, we verified the safety of the vaccine. DFS in 2 years were 56.0% and 58.3% in the vaccine arm and in the control, respectively. Twenty-four of 25 patients showed NY-ESO-1-specific IgG responses after vaccination. Analysis of intra-cohort correlations among vaccinated patients revealed that 5% or greater expression of NY-ESO-1 was a favorable factor. Comprehensive analysis of gene expression profiles revealed that the expression of the gene encoding polymeric immunoglobulin receptor (PIGR) in tumors had a significantly favorable impact on outcomes in the vaccinated cohort. The high PIGR-expressing tumors that had higher NY-ESO-1-specific IgA response tended to have favorable prognosis. These results suggest that PIGR would play a major role in tumor immunity in an antigen-specific manner during NY-ESO-1 vaccinations. The IgA response may be relevant.

Survival benefit of conversion surgery for patients with initially unresectable pancreatic cancer who responded favorably to nonsurgical treatment.

BACKGROUND: Conversion surgery (CS) is expected as a new therapeutic strategy for patients with unresectable pancreatic cancer (UR-PC). We analyzed outcomes of CS for patients with UR-PC and evaluated the survival benefit of CS. METHODS: Thirty-four patients diagnosed with UR-PC according to the National Comprehensive Cancer Network guideline underwent CS in our hospital. Resectability was considered by multimodal images in patients who underwent nonsurgical treatment (NST) for more than 6 months. CS was performed only in patients who were judged to be able to undergo R0 resection. RESULTS: Twenty-six patients had locally advanced PC, and eight had distant metastases. The median duration of NST was 9 (range 5-44) months. R0 resection was achieved in 30 patients (88.2%). Six patients (17.6%) showed Evans grade ≥III. Three- and 5-year overall survival (OS) rates from initial treatment were 74% and 56.9%, respectively, with median survival time (MST) of 5.3 years. The actual 5-year OS rate in 19 patients was 47.4% with an MST of 4.0 years. Patients with Evans grade ≥III had a better prognosis than those with Evans grade

The immunological impact of neoadjuvant chemotherapy on the tumor microenvironment of esophageal squamous cell carcinoma.

BACKGROUND: Esophageal cancer is an aggressive cancer with poor prognosis. However, little is known about the immune response in the tumor microenvironment after neoadjuvant chemotherapy. PURPOSE: To investigate the immunological impact of neoadjuvant chemotherapy in the tumor microenvironment of esophageal squamous cell carcinoma. METHODS: Eighteen patients with esophageal squamous cell carcinoma with and without neoadjuvant chemotherapy were analyzed using immunohistochemical methods for human leukocyte antigen (HLA) class I heavy chain, CD4-, CD8-, and Foxp3-positive cell infiltration. RESULTS: The number of CD4 T cells in the stroma and within the cancer nest was significantly higher in the neoadjuvant chemotherapy group. The number of CD8 T cells in the stroma was significantly higher in the neoadjuvant chemotherapy group. HLA class I expression was more downregulated in the control group compared with the neoadjuvant chemotherapy group. CONCLUSION: Neoadjuvant chemotherapy utilizing 5-fluorouracil and cisplatin in esophageal squamous cell carcinoma is useful to induce CD4 and CD8 T lymphocytes in the tumor microenvironment and to maintain HLA class I expression levels in combination with its direct cytotoxic effects.