The dynamic changes of myeloid derived suppressor cells and tumor associated macrophages in Panc02 pancreatic cancer bearing immunocompetent mice

Objective To establish an immunocompetent pancreatic cancer bearing mice model and clarify the dynamic changes of the CD11b+ GR-1 + myeloid derived suppressor cells (MDSC),CD11 b + Ly6Clow Ly6G + polymorphonuclear myeloid derived suppressor cells (PMN-MDSC) and CD1 1b + Ly6C + Ly6G-monocytic myeloid derived suppressor cells (Mo-MDSC),F4/80+ tumor associated macrophages (TAM) and F4/80 + CD16/32 + CD206-classical activated macrophages (M1),F4/80 + CD16/32-CD206 + adaptive activated macrophages (M2) in pancreatic cancer bearing mice.Methods The C57B6/J mice syngeneic pancreatic adenocarcinoma cell line Panc02 ceils were subcutaneously implanted to establish the immunocompetent murine pancreatic cancer bearing model.According to the tumor size,it was divided into four stages,named T1-T4.The flow cytometry (FCM) was performed to identify the different cell populations.Results With tumor progression,the MDSC population was consistently increased [for peripheral blood,T1 vs.T4,(4.95 ±1.03)％ vs.(36.45 ±6.43)％,P＜0.01; for tumor tissue,T1 vs.T4,(2.95 ± 2.95) ％ vs.(18.17 ± 3.30) ％,P ＜ 0.01],and the PMN-MDSC was the main subpopulation and dramatically increased [for peripheral blood,T1 vs.T4,(29.73 ± 10.30) ％ vs.(66.40 ± 12.10)％,P＜0.01; for tumor tissue,T1 vs.T4,(24.73±10.81)％ vs.(73.17±10.81)％,P＜ 0.01],but the other subtype Mo-MDSC did not significantly change [for peripheral blood,T1 vs.T4,(10.30 ± 1.90) ％ vs.(9.87 ± 1.91) ％,P ＞ 0.05 ; for tumor tissue,T1 vs.T4,(9.10 ± 1.01) ％ vs.(9.90 ±2.21)％,P ＞0.05].The TAM in peripheral blood in T1-T3 stages was consistently increased,including both M1 and M2 [for M1,T1 vs.T3,(6.30 ± 1.25) ％ vs.(20.17 ±2.31) ％,P ＜0.01 ; for M2,(0.87 ± 0.21) ％ vs.(5.40 ± 0.85) ％,P ＜ 0.01],but the M2/M1 ratio became bigger.The peripheral blood macrophages in T4 stage were dramatically declined [T3 vs.T4,(20.17 ± 2.31) ％ vs.(10.77 ± 1.52) ％,P ＜0.01],but M2 was still increased [T3 vs.T4,(6.80 ± 0.75) ％ vs.(8.97 ± 1.20)％,P ＜0.05].The intratumoral M2 tumor associated macrophages were consistently increased [T1 vs.T4,(2.94 ±0.51)％ vs.(13.44 ±2.95)％,P＜0.01],but the M1 did not significantly change [T1 vs.T4,(6.49 ± 1.39) ％ vs.(7.26 ± 1.96) ％,P ＞ 0.05].The ratio of M2/M1 was bigger than that of peripheral blood at the same stage.Conclusion The PMN-MDSC × M2/M1 ratio in peripheral blood and tumor tissue is the formidable surrogate for the tumor burden of pancreatic cancer bearing mice and can be used as a predictor for the prognosis of patients with pancreatic cancer. Key words: Pancreatic cancer;  Myeloid derived suppressor cells;  Tumor associated macrophages ;  Prognosis