Boehm Dylan T, Landreth Kaitlyn M, Kilic Emel Sen, Lee Katherine S, Misra Bishal, Bobbala Sharan, Damron F Heath, Liu Tracy W
Department of Microbiology, Immunology, and Cell Biology, West Virginia University, 64 Medical Center Drive, Morgantown, WV, 26506, USA.
Vaccine Development Center at West Virginia University Health Sciences Center, Morgantown, WV, USA.
Sci Rep. 2025 Feb 13;15(1):5337. doi: 10.1038/s41598-025-89930-0.
Immunotherapies are effective for cancer treatment but are limited in 'cold' tumor microenvironments due to a lack of infiltrating CD8 T cells, key players in the anti-cancer immune response. The onset of the COVID-19 pandemic sparked the widespread use of mRNA-formulated vaccines and is well documented that vaccination induces a Th1-skewed immune response. Here, we evaluated the effects of an intratumoral injection of the mRNA COVID-19 vaccine in subcutaneous melanoma tumor mouse models. Tumor growth and survival studies following a single intratumoral injection of the COVID-19 vaccine showed significant tumor suppression and prolonged survival in established B16F10 subcutaneous tumor-bearing mice. mRNA vaccine treatment resulted in a significant increase in CD8 T cell infiltration into the tumor microenvironment, as observed using intravital imaging and flow cytometry. Further tumor growth suppression was achieved using additional mRNA vaccine treatments. Combination administration of mRNA vaccine with immune checkpoint therapies demonstrated enhanced effects, further delaying tumor growth and improving the survival time of tumor-bearing mice. This study demonstrates that mRNA vaccines may be used as adjuvants for immunotherapies.
免疫疗法对癌症治疗有效，但在“冷”肿瘤微环境中却受到限制，因为缺乏浸润性CD8 T细胞，而CD8 T细胞是抗癌免疫反应的关键参与者。新冠疫情的爆发促使mRNA疫苗广泛使用，并且有充分记录表明接种疫苗会诱导Th1偏向的免疫反应。在此，我们评估了在皮下黑色素瘤肿瘤小鼠模型中瘤内注射mRNA新冠疫苗的效果。在已建立的B16F10皮下荷瘤小鼠中，单次瘤内注射新冠疫苗后的肿瘤生长和生存研究显示出显著的肿瘤抑制作用并延长了生存期。如通过活体成像和流式细胞术所观察到的，mRNA疫苗治疗导致肿瘤微环境中CD8 T细胞浸润显著增加。使用额外的mRNA疫苗治疗进一步实现了肿瘤生长抑制。mRNA疫苗与免疫检查点疗法联合给药显示出增强的效果，进一步延缓了肿瘤生长并改善了荷瘤小鼠的生存时间。这项研究表明，mRNA疫苗可用作免疫疗法的佐剂。
