Das Satyajit, Banerjee Kaushik, Roy Susmita, Majumder Saikat, Chatterjee Mitali, Majumdar Subrata, Choudhuri Soumitra Kumar
Department of In Vitro Carcinogenesis and Cellular Chemotherapy, Chittaranjan National Cancer Institute, Kolkata, India.
Department of Pharmacology, Institute of Postgraduate Medical Education and Research, Kolkata, India.
In Vivo. 2014 Sep-Oct;28(5):909-18.
The tumor microenvironment (TME) renders tumor cells more resistant to chemotherapy. However, effective immunomodulators for cancer therapy are still elusive. We hypothesized that Mn-N-(2-hydroxyacetophenone) glycinate (MnNG), reported to be an antitumor agent, can modulate the TME.
Immunomodulatory effects of MnNG were performed through assessing Myeloid Derived Suppressor Cells (MDSCs), Interferon-γ (Ifnγ)- and Interleukin-4 (Il4)-secreting Cluster of Differentiation 4 (Cd4)(+) T-cells by annexin V-binding assay in drug-resistant TME and T-cell proliferation following in vitro co-culture assay by flow cytometry.
MnNG induced infiltration of Ifnγ-secreting Cd4(+) T-cells and reduces MDSC numbers in vivo. Furthermore, it modulated differentiation of MDSCs towards dendritic cells with up-regulation of co-stimulatory molecules and reversed the suppressive function of MDSC's that enhances T-helper cell 1 (Th1) response. MnNG treatment resulted in reduced expression of IL4, but enhanced expression of Ifnγ when Cd4(+) T-cells were co-cultured with MDSCs.
MnNG modulates MDSCs differentiaton towards dendritic cells and enhances Th1 response in drug-resistant TME, leading to immunomodulatory efficacy.
肿瘤微环境（TME）使肿瘤细胞对化疗更具抗性。然而，用于癌症治疗的有效免疫调节剂仍然难以捉摸。我们假设据报道为抗肿瘤剂的甘氨酸锰-N-（2-羟基苯乙酮）（MnNG）可以调节肿瘤微环境。
通过在耐药肿瘤微环境中利用膜联蛋白V结合试验评估髓源性抑制细胞（MDSC）、分泌干扰素-γ（Ifnγ）和白细胞介素-4（Il4）的分化簇4（Cd4）（+）T细胞，以及通过流式细胞术体外共培养试验后的T细胞增殖，来研究MnNG的免疫调节作用。
MnNG在体内诱导分泌Ifnγ的Cd4（+）T细胞浸润并减少MDSC数量。此外，它调节MDSC向树突状细胞的分化，上调共刺激分子，并逆转MDSC增强辅助性T细胞1（Th1）反应的抑制功能。当Cd4（+）T细胞与MDSC共培养时，MnNG处理导致IL4表达降低，但Ifnγ表达增强。
MnNG调节MDSC向树突状细胞的分化，并增强耐药肿瘤微环境中的Th1反应，从而产生免疫调节功效。
