The induction of tumor‐specific CD4+ T cells via major histocompatibility complex class II is required to gain optimal anti‐tumor immunity against B16 melanoma cell line in tumor immunotherapy using dendritic cells
The induction of tumor‐specific CD4+ T cells via major histocompatibility complex class II is required to gain optimal anti‐tumor immunity against B16 melanoma cell line in tumor immunotherapy using dendritic cells
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DOI：
10.1111/j.1600-0625.2008.00802.x
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发表时间：
2009-04
影响因子：
3.6
通讯作者：
Y. Fujisawa;T. Nabekura;Tomohei Nakao;Yasuhiro Nakamura;Takenori Takahashi;Y. Kawachi;F. Otsuka;M. Onodera
中科院分区：
文献类型：
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作者：
Y. Fujisawa;T. Nabekura;Tomohei Nakao;Yasuhiro Nakamura;Takenori Takahashi;Y. Kawachi;F. Otsuka;M. Onodera
摘要：我们已经证明，用逆转录病毒载体遗传修饰以表达肿瘤相关抗原（TAA）的树突状细胞（DC）比负载肽的树突状细胞（DC）引起更潜在的抗肿瘤作用，因为它们可以引发抗原特异性CD 4 + T细胞，从而产生肿瘤特异性抗体。在这项研究中，我们通过使用来自MHC II类缺陷小鼠（C2 KO）的DC，证明了通过主要组织相容性复合体（MHC）II类分子进行抗原呈递在针对非膜结合TAA（如黑素瘤抗原gp 100）的癌症免疫中的重要性。通过将gp 100 cDNA转导至从C2 KO获得的造血祖细胞中，随后用细胞因子分化来制备DC（C2 KO-gp/DC）。当将C2 KO ‐gp/DCs接种到免疫活性小鼠中时，小鼠几乎没有引发抗原特异性Th 1细胞，并且比接种从正常小鼠制备的转导的DCs的小鼠产生更少的CD 8 T细胞。在免疫后环境中也证实了减弱的抗肿瘤作用，其中8只对照小鼠中有2只根除了预先存在的黑色素瘤细胞系B16（25%），而接种C2 KO-gp/DC的小鼠则没有。这些结果不仅表明了目前使用MHC I类限制性肿瘤肽的方案的局限性，而且还表明了表达gp 100的DC在针对黑素瘤的疫苗治疗中的有用性。
Abstract: We have demonstrated that dendritic cells (DCs) genetically modified to express tumor‐associated antigens (TAAs) with retroviral vectors elicit more potential anti‐tumor effect than those loaded with peptides because they can prime antigen‐specific CD4+ T cells resulting in production of tumor‐specific antibody. In this study, we showed the importance of antigen presentation via a major histocompatibility complex (MHC) class II molecule in cancer immunity against non‐membrane bound TAAs such as the melanoma antigen gp100 by using DCs derived from MHC class II‐deficient mice (C2KO). DCs were prepared by transduction of gp100 cDNA into haematopoietic progenitor cells obtained from C2KO followed by differentiation with cytokines (C2KO‐gp/DCs). When C2KO‐gp/DCs were inoculated into immunocompetent mice, the mice scarcely primed the antigen‐specific Th1 cells and developed fewer CD8 T cells than did those inoculated with transduced DCs prepared from normal mice. The attenuated anti‐tumor effect was also confirmed in a postimmunization setting where, while two of eight control mice eradicated the pre‐existing melanoma cell line B16 (25%), no mice inoculated with C2KO‐gp/DCs did. These results suggested not only the limitation of current protocols using MHC class I‐restricted tumor peptides but also the usefulness of DCs expressing gp100 in vaccine therapy against melanoma.