化疗是胰腺癌最主要的治疗方法之一。化疗药物在杀灭肿瘤细胞的同时也可引起肿瘤免疫微环境的改变，从而影响化疗效果。吉西他滨是胰腺癌的一线化疗药物，但人们对其引起的肿瘤免疫微环境的变化还知之甚少。我们前期工作发现：吉西他滨化疗后肿瘤组织中Th2型细胞因子表达升高以及M2型肿瘤相关巨噬细胞（TAM）增多；胰腺癌组织中免疫球蛋白G4（IgG4）阳性浆细胞明显多于癌旁组织，是预后不良的独立危险因素；胰腺癌组织内IgG4阳性浆细胞与M2型TAM分布有明显的线性相关性。已有研究报道Th2型细胞因子可诱导IgG4，且IgG4可抑制TAM的功能。故我们拟进一步探讨吉西他滨化疗诱导的胰腺癌免疫微环境的变化，特别是胰腺癌细胞、TAM以及IgG4阳性浆细胞之间潜在的调控网络及分子机制，为提高吉西他滨的化疗疗效提供新的靶点，为胰腺癌的综合治疗提供新的思路。

Chemotherapy is one of the main treatments for pancreatic cancer. When the chemotherapeutic drugs kill cancer cells, they will also change the tumor immune microenvironment which will affect the efficacy. Gemcitabine is the first line chemotherapeutic drug for pancreatic cancer, however the changes of tumor immune microenvironment induced by gemcitabine remain largely unknown. We have previously found: gemcitabine could induce Th2 type cytokines and M2 polarized tumor associated macrophages; there were more immunoglobulin G4(IgG4) positive plasma cells in tumor tissue than that in the peritumoral tissue, and the intratumoral IgG4 positive plasma cell is an independent risk factor for poor prognosis of pancreatic cancer; Intratumoral IgG4 positive plasma cells are positively linear correlated with M2 polarized TAM. It has been reported that Th2 type cytokines could induce IgG4 and IgG4 could inhibit the activation of macrophages. We will further explore the gemcitabine –induced immune microenvironment of pancreatic cancer, especially the network and molecular mechanisms of pancreatic cancer cells, TAM and IgG4 positive plasma cells, to seek the new targets to improve the efficacy of gemcitabine and present new strategies of integrated treatments of pancreatic cancer.