Abstract B70: Differential expression of regulatory T cells and Th17 cells are indicative of tumor recurrence in pN0 stage I lung cancer patients

Abstract

Abstract Background: Up to 30% of lung cancer (Stage I) with the most favorable outcome recur within 5 years after surgery. Predicting relapse in patients treated curatively with surgical resection for stage I non-small cell lung cancer (NSCLC) remains difficult. The sentinel lymph nodes (SLNs) are the first lymph nodes reached by metastatic cancer cells from a primary tumor. In a recent immunologic study, immunologic changes were detected in these lymph nodes prior to pathologic invasion. This study evaluated the pattern of failure after surgical resection in pN0 lung cancers and determines whether regulatory T (Treg) cells and Th17 cells were prognostic indicator for recurrence. Methods: Patients over 18 years of age who were clinically diagnosed with stage I lung cancer were enrolled. Patients receiving prior lung cancer treatment or thoracic radiation were excluded from enrollment. During surgery, the sentinel lymph nodes were isolated using a handheld gamma probe, followed by the dissection of the visible mediastinal, hilar, and peribronchial lymph nodes. Samples from normal lung tissue, the tumor mass, and all dissected lymph nodes were sectioned and conventionally examined using H&E staining and immunohistochemistry. In addition, the forkhead transcription factor3 (Foxp3) and transcription factor retinoic acid-related orphan receptor (ROR)-γ, recently described to be essential for differentiation of Tregs and Th17 cells, were evaluated by real time RT-PCR. Results: Between October 2009 and October 2010, 27 patients with clinical stage I NSCLC were enrolled consecutively. Among them, twenty patients (thirteen men, seven women, mean age 67.6 years) pathologically staged as N0 were analyzed. Eight patients had squamous cell carcinoma and twelve patients had adenocarcinoma. The expression of Foxp3 in the tumor mass was increased in adenocarcinoma compared to squamous cell carcinoma (P=0.05). The Foxp3 expression and Treg cells in the tumor mass were not significantly associated with recurrence. However, Foxp3 expression and Treg cells’ presence in SLNs were significantly increased in patients with recurring disease compared to nonrecurring disease (P=0.03 and P=0.01, respectively). The number of Th17 cells in tumor mass was decreased in patients with recurring pN0 disease compared to those with non-recurring disease (P=0.04). ROR-γ expression and Th17 cells presence in SLNs were not related with recurrence. Conclusion: The results of this study suggest that the increased number of Treg cells in SLNs and decreased number of Th17 cells in tumor mass might be a promising indicator of recurrence. Citation Format: Chan Kwon Park, Seung Joon Kim. Differential expression of regulatory T cells and Th17 cells are indicative of tumor recurrence in pN0 stage I lung cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr B70.