Cell Biology Laboratory, Hoag Cancer Center, 1 Hoag Drive Bldg 41, 92663, Newport Beach, CA, USA.
Cancer Immunol Immunother. 2011 Jan;60(1):123-31. doi: 10.1007/s00262-010-0925-y. Epub 2010 Oct 20.
The use of whole cell tumor vaccines and various means of loading antigen onto dendritic cells have been under investigation for over a decade. Induction of apoptosis and the exposure of immune-stimulating proteins are thought to be beneficial for the use in immunotherapy protocols, but conclusive evidence in the clinical setting has been lacking. Incubation of melanoma cell lines with interferon-gamma (IFN-γ) increased phosphatidylserine and calreticulin exposure, but not in the IFN-γ-resistant cell line Lu-1205. Short-term autologous melanoma cell lines used for loading dendritic cells for immunotherapy showed differential response to the pro-apoptotic effects of IFN-γ. These IFN-γ-treated tumor cells (TCs) were irradiated and used for loading antigen for dendritic cell therapy. A log-rank comparison of survival for patients whose TCs were found to be either sensitive (upregulated phosphatidylserine and calreticulin) or insensitive to IFN-γ revealed a strongly significant correlation to progression-free (p = 0.003) and overall survival (p = 0.002) favorably in those patients whose cell lines were resistant to the proapoptotic effect of IFN-γ. These results suggest that the use of IFN-γ in anti-melanoma dendritic cell-based immunotherapy may only be beneficial when the cells do not undergo apoptosis in response to IFN-γ and support the contention that the use of some apoptotic cells in vaccines may be detrimental.
十多年来，人们一直在研究使用全肿瘤细胞疫苗和各种方法将抗原加载到树突状细胞上。诱导细胞凋亡和暴露免疫刺激蛋白被认为有利于免疫治疗方案的应用，但在临床环境中缺乏确凿的证据。用干扰素-γ（IFN-γ）孵育黑色素瘤细胞系增加了磷脂酰丝氨酸和钙网蛋白的暴露，但在 IFN-γ 抗性细胞系 Lu-1205 中则没有。用于加载树突状细胞进行免疫治疗的短期自体黑色素瘤细胞系对 IFN-γ 的促凋亡作用表现出不同的反应。这些经 IFN-γ 处理的肿瘤细胞（TCs）经过照射，用于加载抗原用于树突状细胞治疗。对 TCs 被发现对 IFN-γ 敏感（上调磷脂酰丝氨酸和钙网蛋白）或不敏感的患者进行生存对数秩比较，结果显示对无进展（p=0.003）和总生存（p=0.002）有强烈的显著相关性，这对那些细胞系对 IFN-γ 的促凋亡作用具有抗性的患者有利。这些结果表明，在抗黑色素瘤树突状细胞为基础的免疫治疗中使用 IFN-γ 可能只有在细胞不因 IFN-γ 而发生凋亡时才有益，并支持在疫苗中使用一些凋亡细胞可能有害的观点。
