Abstract
e21006 Background: Myeloid derived suppressor cell (MDSC) and regulatory T cell (Treg) accumulation in cancer patients is proposed as an important mechanism of tumor immune evasion. We present for the first-time analysis of both MDSCs and Tregs in pancreatic and esophago-gastric cancer. Methods: Peripheral blood samples were collected from 35 pancreatic, 46 esophageal and 19 gastric cancer patients and 31 normal healthy volunteers. PBMC was harvested and stored in liquid N2 with subsequent flow cytometric analysis of MDSC (HLADR- Lin1- CD33+ CD11b+) and Treg (CD4+ CD25+ CD127low/- FoxP3+). Unpaired T tests were applied to analyse MDSC and Treg levels between groups. Kaplan-Meier survival analysis was performed to compare patients with normal MDSC levels (as defined by the controls range, 0%-2% total PBMCs) and high MDSCs (> 2%). Results: The mean percentage of MDSCs in each cancer group was significantly higher than controls; pancreatic 2.455% (p = 0.0005), esophageal 1.623% (p = 0.0260) and gastric 2.029% (p = 0.0326), with controls 1.104%. Pancreatic and esophago-gastric cancer patients had significantly higher mean Treg percentages than controls, p = 0.0036 and p = 0.0189 respectively. There was a significant positive correlation between upper GI cancer patients' MDSC and Treg scores (Spearman's rho +0.285; p = 0.008). Patients with normal MDSC levels survived longer than those with high levels (log rank: p = 0.011), median survival 231 vs. 145 days. The influence of MDSC score was further quantified by Cox regression analysis with MDSC score as a covariate: p < 0.0005. Treg percentage was not significantly associated with survival. Conclusions: Pancreatic and esophago-gastric cancer patients have elevated MDSC correlating with poor prognosis, indicating MDSCs as a potential biomarker for survival. We will present this data with further analysis of the longitudinal impact of chemotherapy and immunotherapy on number and function of MDSCs and Tregs in order to assess the augmentation by chemotherapy of responses to immunotherapy. No significant financial relationships to disclose.
Published Version
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