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Regulatory T-cell subpopulations in patients with pulmonary adenocarcinoma

Phillips JD, Blatner NR, DeCamp MM, Heiferman J, Milad H, Bentrem D, Khazaie K. Regulatory T-cell subpopulations in patients with pulmonary adenocarcinoma. Paper presented at: Academic Surgical Congress; 2012 Feb 15; Las Vegas, NV.

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Introduction: Lung cancer is the most commonly diagnosed malignancy and the leading cause of cancer-related death worldwide. Because of the potential for immunomodulation as a therapeutic modality, the interactions between lung cancer cells and the immune system is currently an area of intense research. Regulatory T-cells (Treg), defined as CD4+CD25+Foxp3+, are an integral component of immune regulation against autoimmunity, and may permit cancer cells to evade the host immune response. Sakaguchi et al. have recently described functionally distinct subpopulations of Treg: I (resting Treg), II (activated Treg), and III (cells with Th17 pro-inflammatory potential). These subpopulations exist in different proportions in healthy donors and patients with benign inflammatory diseases, such as sarcoidosis and lupus. The aim of this study was to determine if these sub-populations exist in differential proportions in patients with pulmonary adenocarcinoma. Methods: Peripheral blood was collected from healthy donors and patients undergoing surgical resection for suspected pulmonary adenocarcinoma. Total mononuclear cells were isolated via gradient centrifugation and stained with cellular markers for CD4, CD25, Foxp3, RORgt, CD103, ICOS, CD45RA, CD45RO, HLA-DR, CXCR3, CCR6, Ki67, and Annexin V. Fluorescent Activated Cell Sorting analysis was performed and population frequencies calculated. Statistical analysis was performed using the Kruskal-Wallis test and p < 0.05 was considered significant. Results: Samples were collected from 23 healthy donors and 16 patients with histologically confirmed pulmonary adenocarcinoma. Lung cancer patients had a significantly increased proportion of population II, 18.49% vs. 3.17% (p < 0.001). This subpopulation also had increased expression of ROR t and CCR9, and decreased expression of ICOS, CD103, and CCR6. No significant differences in the frequency of population I or III were observed. Conclusions: Patients with lung adenocarcinoma have an increased proportion of activated Treg in their peripheral blood compared to healthy donors. In addition, these cells have differing expression of several cellular makers compared to the same population in healthy donors. To our knowledge, this is the first evidence of the differential proportion of activated Treg subpopulations in lung cancer patients. Thus, these cells may serve as a potential therapeutic target for immunomodulation in the treatment of lung cancer. Further research is needed to delineate the functional affects these subpopulations have on lung adenocarcinoma.

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