Event Abstract Back to Event MYELOID-DERIVED SUPPRESSOR CELLS IN LUNG CANCER Renato Morales1*, Lourdes Barrera1, Isabel Sada1, Angelica Rodríguez1 and Oscar Arrieta2 1 Instituto Nacional de Enfermedades Respiratorias, Departamento de Investigación, Mexico 2 Instituto Nacional de Cancerología, Clínica de Cáncer de Pulmon, Mexico BACKGROUND: Lung cancer (LC) is the most frequent cause of cancer death in men and women worldwide; in 2012 nearly 1.8 million cases and 1.6 million deaths occurred with adenocarcinoma being the most common histological subtype. Despite the novel advances in therapy, only 16.6% of patients with LC remain alive five years after diagnosis. At the beginning of the disease tumor cells try to evade the immune response through several mechanisms comprising the release of soluble factors and immunomodulatory molecules that promotes the recruitment and development of immunosuppressive cells. Immune cells involved in this phenomenon are regulatory T cells and myeloid suppressor cells (MSC). The latter are a heterogeneous population of cells induced during states of chronic inflammation such as cancer, they are recruited and tend to accumulate in peripheral blood and lymphoid organs. MSC limits the immune response against tumoral cells trough several mechanisms including: a) the molecular modifications at the T cell receptor level, b) induction of apoptosis and development of an exhausted T cell phenotype, c) induction of regulatory T cells and d) generation of chronic inflammation. Some of these immune alterations have been described in the mouse model but not in patients with LC. However MSC have been also used in other types of cancer as a marker of survival, recurrence, metastasis, stage of dieses and treatment response among others. Our group has previously shown in LC patients an increase in the frequency CD11b+CD14-CD15+CD66b+ Granulocyte-MSC (G-MSC). We also identified a decrease in the frequency of total CD3+ T cells, CD8+ T cells and a reduction in expression of their CD3 receptor Z chain. These findings suggest that the immune dysfunction observed in LC patients may be partially explained by the presence of the MSC population that limits proper T cell function. HIPOTHESIS: Patients with LC will have an increased frequency of CD11b+CD14-CD15+CD66b+ (G-MSC) that reduces the CD3 receptor Z chain expression on total T cells. OBJETIVE: Evaluate the frequency of G-MSC and the CD3 receptor Z chain expression profile on total T cells from LC patients. RESULTS: The main results of our study are: 1) the frequency of G-MSC was increased in LC patients (9.2% ± 3.9), when compared with healthy donors (3.2% ± 0.9) (p<0.001), 2) the frequency of total T cells was decreased in LC patients (46.9% ± 11), when compared with healthy donors (28.2% ± 13) (p<0.001), 3) the expression of the CD3 receptor Z chain is decreased in T cells from LC patients (3096 [1194-7793]), when compared with healthy donors (9982 [1002-13465]) (p<0.001). DISCUSION: In recent years an important role of MSC in tumor-associated immune suppression has been established in a large number of studies. Besides cancer, an increased production of MSC has been reported in a number of pathological conditions including traumatic stress and bacterial and parasitic infections. They do not represent a single cell subset but in fact are comprised of immature myeloid cells at different stages of cell differentiation. The characterization of G-MSC and their potential impact in impaired T cell responses primarily responsible for tumor-associated immune suppression is critical for understanding the biology of these cells and the mechanisms of tumor escape in LC patients. To address this issue, we first analyzed the frequency and phenotype of G-MSC and next established an in vitro experimental model were enriched CD8+ T cells were co-cultured with autologous G-MSC. We found that the level of MSC was significantly elevated in LC patients and the frequency of total CD3+ T cells was reduced when compared with healthy donors. Detailed cytometric analysis of CD8+ T cells cultured with G-MSC made evident the reduced expression of CD3 receptor Z chain suggesting this might be one potential mechanism of immune impairment in LC patients. Our preliminary data demonstrated that G-MSC population limits the T cell functional activation as a mechanism of T cell suppression. More studies are needed to clarify exact role of this and other specific mechanisms mediating immune suppression by these MSC subsets.