Kaitlyn Fessler, Jiaqi Zhang, Avinaash K Sandhu, Yinan Hui, Aakanksha R Kapoor, Samuel K Ayeh, Styliani Karanika, Petros C Karakousis, Richard B Markham, James T Gordy
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引用次数: 0
摘要
先前在 B16F10 小鼠黑色素瘤模型中进行的研究表明,将由 gp100 和酪氨酸酶相关蛋白 2 与巨噬细胞炎症蛋白 3-α (MIP3α) 融合的区域组成的 DNA 疫苗与重组干扰素 alpha (IFN) 和 5-Aza-2'-deoxycytidine (5Aza) 处理相结合,可显著提高抗肿瘤活性和肿瘤微环境 (TME) 中的免疫原性。本简短报告详细介绍了疫苗与 IFN 和 5Aza 治疗的结合会导致肿瘤微环境中一种独特的 CD11c+ CD8+ T 细胞群的增加。这种细胞群与肿瘤大小相关,主要由效应或效应记忆 T 细胞组成,与 CD11c- CD8+ T 细胞相比,对体内外刺激的反应更强。总之,这种联合疗法能在TME中产生更多表达CD11c的高活性效应CD8+ T细胞,这可能是疗效的主要因素。
Brief Communication: Combination of an MIP3α-Antigen Fusion Therapeutic DNA Vaccine With Treatments of IFNα and 5-Aza-2'Deoxycytidine Enhances Activated Effector CD8+ T Cells Expressing CD11c in the B16F10 Melanoma Model.
Previous studies in the B16F10 mouse melanoma model have demonstrated that combining a DNA vaccine comprised of regions of gp100 and tyrosinase-related protein 2 fused to macrophage-inflammatory protein 3-alpha (MIP3α) with recombinant interferon alpha (IFN) and 5-Aza-2'-deoxycytidine (5Aza) treatments resulted in significantly greater antitumor activity and immunogenicity in the tumor microenvironment (TME). This brief report details that the combination of vaccine with treatments IFN and 5Aza results in an increase in the TME of a distinct CD11c+ CD8+ T-cell population. This cell population correlates with tumor size, is primarily comprised of effector or effector memory T cells, and has a more robust response to ex vivo stimulation as compared with CD11c- CD8+ T cells. In conclusion, this combination therapy results in a greater presence of highly active effector CD8+ T cells expressing CD11c in the TME, which are likely primary contributors to treatment efficacy.
期刊介绍:
Journal of Immunotherapy features rapid publication of articles on immunomodulators, lymphokines, antibodies, cells, and cell products in cancer biology and therapy. Laboratory and preclinical studies, as well as investigative clinical reports, are presented. The journal emphasizes basic mechanisms and methods for the rapid transfer of technology from the laboratory to the clinic. JIT contains full-length articles, review articles, and short communications.