Nature：IgG抗体对肿瘤的排斥

    癌症通常会躲避主体免疫反应，但肿瘤却不会在不同个体之间传播，这说明免疫系统没有识别和杀死肿瘤细胞的能力。对小鼠移植的同种异体肿瘤的命运所做的这项研究显示，它们的排斥是由自然出现的肿瘤结合型IgG抗体启动的。肿瘤免疫复合物在Fcγ-受体介导下向树突细胞中的吸收会激发肿瘤反应性T-细胞，同种异体IgG连同树突细胞助剂的肿瘤内注射，会诱导全身性的、由T-细胞介导的抗肿瘤反应。这项工作揭示了也许可以在临床上加以利用的一个新的肿瘤排斥机制。

    原文链接：Allogeneic IgG combined with dendritic cell stimuli induce antitumour T-cell immunity

    原文摘要：wheras cancers grow within host tissues and evade host immunity through immune-editing and immunosuppression1, 2, 3, 4, 5, tumours are rarely transmissible between individuals. Much like transplanted allogeneic organs, allogeneic tumours are reliably rejected by host T cells, even when the tumour and host share the same major histocompatibility complex alleles, the most potent determinants of transplant rejection6, 7, 8, 9, 10. How such tumour-eradicating immunity is initiated remains unknown, although elucidating this process could provide the basis for inducing similar responses against naturally arising tumours. Here we find that allogeneic tumour rejection is initiated in mice by naturally occurring tumour-binding IgG antibodies, which enable dendritic cells (DCs) to internalize tumour antigens and subsequently activate tumour-reactive T cells. We exploited this mechanism to treat autologous and autochthonous tumours successfully. Either systemic administration of DCs loaded with allogeneic-IgG-coated tumour cells or intratumoral injection of allogeneic IgG in combination with DC stimuli induced potent T-cell-mediated antitumour immune responses, resulting in tumour eradication in mouse models of melanoma, pancreas, lung and breast cancer. Moreover, this strategy led to eradication of distant tumours and metastases, as well as the injected primary tumours. To assess the clinical relevance of these findings, we studied antibodies and cells from patients with lung cancer. T cells from these patients responded vigorously to autologous tumour antigens after culture with allogeneic-IgG-loaded DCs, recapitulating our findings in mice. These results reveal that tumour-binding allogeneic IgG can induce powerful antitumour immunity that can be exploited for cancer immunotherapy.