CD4 T cell-mediated masking effects of the immunogenicity of tumor-associated antigens are qualitatively and quantitatively different depending on the individual antigens.
CD4 T cell-mediated masking effects of the immunogenicity of tumor-associated antigens are qualitatively and quantitatively different depending on the individual antigens.
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发表时间：
2013
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通讯作者：
S. Okano;Yoshihiro Matsumoto;S. Yoshiya;Y. Yamashita;N. Harimoto;T. Ikegami;K. Shirabe;M. Harada;Y. Yoshikai;Y. Maehara
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作者：
S. Okano;Yoshihiro Matsumoto;S. Yoshiya;Y. Yamashita;N. Harimoto;T. Ikegami;K. Shirabe;M. Harada;Y. Yoshikai;Y. Maehara
将癌症免疫疗法作为多学科治疗癌症的一部分，是治疗晚期癌症患者的一种很有前途的策略。在癌症免疫治疗中，有效启动肿瘤相关抗原（TAA）特异性CD8+ T细胞是必不可少的，因此，适当选择最佳肽靶向癌症是最重要的问题。选择TAA的一个批评是TAA的免疫原性，接种该疫苗可有效地引起临床反应。然而，影响TAAs免疫原性差异的关键基本免疫学因素仍有待阐明。在这里，我们发现CD4 t细胞反应抑制了小鼠黑色素瘤模型中伴随的TAA的免疫原性，其中瘤内活化树突状疗法（ITADT）用于治疗已建立的癌症，我们观察到抗肿瘤作用在很大程度上依赖于CD8 t细胞反应。CD4 t细胞耗竭仅增强酪氨酸酶相关蛋白(TRP)-2（180-188）肽特异性细胞毒性t细胞（CTL）反应，CD4 t细胞耗竭提供了mgp100（25-33）肽的免疫原性，在治疗早期CD4 t细胞完整的小鼠中完全没有检测到CTL反应。此外，在CD4 T细胞恢复后，mgp100（25-33）肽特异性CTL反应再次无法检测到，而在CD4缺失小鼠中，TRP-2（180-188）肽特异性CTL反应仍然比CD4完整小鼠强得多。这些发现表明，CD4 T细胞介导的肿瘤相关抗原免疫原性的掩蔽作用在质量和数量上取决于单个抗原。
The use of cancer immunotherapy as part of multidisciplinary therapies for cancer is a promising strategy for the cure of advanced cancer patients. In cancer immunotherapy, the effective priming of tumor-associated antigen (TAA)-specific CD8+ T cells is essential, and therefore, the appropriate selection of the best peptide for targeting the cancer is a most important concern. One criticism in the selection of a TAA is the immunogenicity of the TAA, the vaccination of which effectively elicits clinical responses. However, the critical basic immunological factors that affect the differences in the immunogenicity of TAAs remain to be elucidated. Here we found that CD4 T-cell responses suppressed the immunogenicity of the concomitant TAA in a murine melanoma model in which intratumoral activated dendritic therapy (ITADT) was used for treatment of the established cancer, and we observed that the antitumor effects were largely dependent on the CD8 T-cell response. CD4 T-cell depletion simply enhanced the tyrosinase-related protein (TRP)-2(180-188) peptide-specific cytotoxic T-cell (CTL) responses, and CD4 T-cell depletion provided immunogenicity for mgp100(25-33) peptide, to which a CTL response could not be detected at all in CD4 T-cell-intact mice in the early therapeutic phase. Further, the mgp100(25-33) peptide-specific CTL response again became undetectable after the recovery of CD4 T cells in previously CD4-depleted, tumor-eradicated mice, whereas the TRP-2(180-188) peptide-specific CTL response was still much stronger in CD4-depleted mice than in CD4-intact mice. These findings suggest that the CD4 T cell-mediated masking effects of the immunogenicity of tumor-associated antigens are qualitatively and quantitatively different depending on the individual antigens.