免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Anti-VEGF immunotherapy with HEBERSaVax suppresses melanoma growth and metastasis via angiogenesis blockade and enhanced T-cell infiltration.
Anti-VEGF immunotherapy with HEBERSaVax suppresses melanoma growth and metastasis via angiogenesis blockade and enhanced T-cell infiltration.
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我们的结果表明,HEBERSaVax 通过同时抑制 VEGF 依赖性血管生成并促进黑色素瘤微环境中的免疫相关变化,介导了双重抗肿瘤疗效。这些发现支持进一步开发 HEBERSaVax 作为一种有前景的针对 VEGF 驱动的晚期黑色素瘤的主动免疫治疗。
通过血管内皮生长因子(VEGF)阻断靶向肿瘤血管生成是黑色素瘤治疗的一种有前景的策略。在此,我们评估了HEBERSaVax——一种抗VEGF主动免疫疗法——在侵袭性B16-F10同系黑色素瘤模型中的治疗潜力。
评估了以磷酸铝佐剂配制的 HEBERSaVax 在 C57BL/6 小鼠中的抗肿瘤活性,采用两种不同的 B16-F10 黑色素瘤模型:(i) 皮下接种以评估原发肿瘤生长抑制,(ii) 静脉接种以量化肺转移抑制。通过免疫组化(CD31、α-SMA、CD4、CD8)分析肿瘤血管和微环境变化。
与佐剂对照组相比,HEBERSaVax显著降低了皮下植入瘤的原发肿瘤体积和重量。组织病理学分析显示其具有强效的血管生成抑制作用,CD31+血管密度降低,并出现血管重塑。在肿瘤控制的同时,我们观察到肿瘤微环境的变化,包括α-SMA+周细胞减少以及CD4+和CD8+ T细胞浸润增加。在转移模型中,HEBERSaVax治疗组小鼠较对照组表现出更少的肺部结节。
The antitumor activity of HEBERSaVax, formulated with aluminum phosphate adjuvant, was evaluated in C57BL/6 mice using two distinct B16-F10 melanoma models (i): subcutaneous inoculation to assess primary tumor growth inhibition, and (ii) intravenous inoculation to quantify lung metastasis suppression. Tumor vasculature and microenvironment changes were analyzed via immunohistochemistry (CD31, α-SMA, CD4, CD8).
HEBERSaVax significantly reduced primary tumor volume and weight in subcutaneous implants compared to adjuvant controls. Histopathological analysis revealed potent angiogenesis inhibition, decreased CD31 + vessel density, and vascular remodeling. Concomitant with tumor control, we observed changes in the tumor microenvironment, including a reduction in α-SMA + pericytes and an increase in the infiltration of CD4 + and CD8 + T cells. In the metastatic model, HEBERSaVax-treated mice showed fewer pulmonary nodules versus controls. DISCUSSION: Our results demonstrate that HEBERSaVax mediates dual antitumor efficacy by simultaneously suppressing VEGF-dependent angiogenesis and promoting immune-related changes in the melanoma microenvironment. These findings support the further development of HEBERSaVax as a promising active immunotherapy for VEGF-driven advanced melanoma.
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