Fessler Kaitlyn, Zhang Jiaqi, Sandhu Avinaash K, Hui Yinan, Kapoor Aakanksha R, Ayeh Samuel K, Karanika Styliani, Karakousis Petros C, Markham Richard B, Gordy James T
Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
Department of Medicine, Division of Infectious Diseases, Center for Tuberculosis Research, The Johns Hopkins Hospital, Baltimore, MD.
J Immunother. 2025 Jan 1;48(1):1-5. doi: 10.1097/CJI.0000000000000542. Epub 2024 Oct 14.
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.
先前在B16F10小鼠黑色素瘤模型中的研究表明，将由gp100和酪氨酸酶相关蛋白2区域与巨噬细胞炎性蛋白3-α（MIP3α）融合而成的DNA疫苗与重组干扰素α（IFN）和5-氮杂-2'-脱氧胞苷（5Aza）联合治疗，在肿瘤微环境（TME）中产生了显著更强的抗肿瘤活性和免疫原性。本简要报告详细阐述了疫苗与IFN和5Aza联合治疗可导致独特的CD11c + CD8 + T细胞群体在TME中增加。该细胞群体与肿瘤大小相关，主要由效应或效应记忆T细胞组成，与CD11c - CD8 + T细胞相比，对体外刺激有更强的反应。总之，这种联合疗法导致在TME中表达CD11c的高活性效应CD8 + T细胞大量存在，这些细胞可能是治疗效果的主要贡献者。
