Expression of New York esophageal squamous cell carcinoma 1 and its association with Foxp3 and indoleamine-2,3-dioxygenase in microenvironment of nonsmall cell lung cancer.

Lung cancer is one of the most prevalent and fatal cancer worldwide. The traditional treatments including surgery, radiotherapy, chemotherapy and targeted therapy are not satisfactory because of severe side effects and/or relapse. Genetically engineered T-cell-based immunotherapy for malignant cancer shows promise in recent clinical trials. T-cell receptor (TCR)-engineered T cells targeting New York esophageal squamous cell carcinoma 1 (NY-ESO-1) have been employed in a number of clinical trials for late stage melanoma, synovial sarcoma, multiple myeloma and other malignancies. Owing to the significant efficacy and controllable side effect, NY-ESO-1 has been considered as one of the most ideal TCR-engineered T cell therapy (TCR-T) cell target for solid tumors, including nonsmall cell lung cancer (NSCLC). However, the incidence of NY-ESO-1 expression and its relationship with immunosuppressive microenvironment of NSCLC are largely unclear. In this study, we analyzed the expression of NY-ESO-1 and two key immune regulators, Forkhead box P3 (Foxp3) and indoleamine-2,3-dioxygenase (IDO), in 156 NSCLC specimens by immunohistochemistry. Our results showed that NY-ESO-1 positive rate is 28.1% (44/156) and significantly higher in distal metastasis (P = 0.012) and late stage (P = 0.019) NSCLC patients. In addition, we found that NY-ESO-1 expression was positively associated with Foxp3 level but not IDO. These findings implied the potential role of NY-ESO-1 in tumor immune escape of NSCLC and indicated the requirement to remove Treg cells in TCR-T cell therapy for NSCLC patients.

Treatment of metastatic non-small cell lung cancer with NY-ESO-1 specific TCR engineered-T cells in a phase I clinical trial: A case report.

This article presented a case of a human leukocyte antigen (HLA)-A2-positive patient with advanced cancer/testis antigen New York esophageal squamous cell carcinoma-1 (NY-ESO-1) expressing lung adenocarcinoma (LADC) who received adoptive cell therapy of T cell receptor engineered-T cells (TCR-T cells) targeting the cancer-testis antigen NY-ESO-1. The appropriate clinical and laboratory assessments were conducted to investigate the safety and efficacy of this therapy for this lung cancer patient. The patient had a clinical response to and was well-tolerated with this therapy in the clinical trial. In addition, a preliminary evaluation of the safety of NY-ESO-1 TCR-T cell therapy was performed in four patients with non-small cell lung cancer (NSCLC) enrolled in a clinical trial. It was well-tolerated and did not observe any serious adverse events post-infusion. Fever, anemia, and a decrease in white blood cell count were common adverse events, which were likely due to the TCR-T cell therapy. Two patients had clinical responses to NY-ESO-1 TCR-T cell therapy, including the 44-year-old female patient with LADC, who achieved a short-term partial response for 4 months, improved in Karnofsky performance status, and had a recovery of drug sensitivity. This suggests that TCR-T cell therapy targeting NY-ESO-1 antigen may be beneficial for HLA-A2-positive late-stage patients with NY-ESO-1-expressing NSCLC.