Germeau Catherine, Ma Wenbin, Schiavetti Francesca, Lurquin Christophe, Henry Emmanuelle, Vigneron Nathalie, Brasseur Francis, Lethé Bernard, De Plaen Etienne, Velu Thierry, Boon Thierry, Coulie Pierre G
Cellular Genetics Unit, Université de Louvain, B-1200 Brussels, Belgium.
J Exp Med. 2005 Jan 17;201(2):241-8. doi: 10.1084/jem.20041379.
After vaccination of melanoma patients with MAGE antigens, we observed that even in the few patients showing tumor regression, the frequency of anti-vaccine T cells in the blood was often either undetectable or <10(-5) of CD8 T cells. This frequency being arguably too low for these cells to be sole effectors of rejection, we reexamined the contribution of T cells recognizing other tumor antigens. The presence of such antitumor T cells in melanoma patients has been widely reported. To begin assessing their contribution to vaccine-induced rejection, we evaluated their blood frequency in five vaccinated patients. The antitumor cytotoxic T lymphocyte (CTL) precursors ranged from 10(-4) to 3 x 10(-3), which is 10-10,000 times higher than the anti-vaccine CTL in the same patient. High frequencies were also observed before vaccination. In a patient showing nearly complete regression after vaccination with a MAGE-3 antigen, we observed a remarkably focused antitumoral response. A majority of CTL precursors (CTLp's) recognized antigens encoded by MAGE-C2, another cancer-germline gene. Others recognized gp100 antigens. CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards. These results suggest that a spontaneous antitumor T cell response, which has become ineffective, can be reawakened by vaccination and contribute to tumor rejection. This notion is reinforced by the frequencies of anti-vaccine and antitumor CTLs observed inside metastases, as presented by Lurquin et al. (Lurquin, C., B. Lethe, V. Corbiere, I. Theate, N. van Baren, P.G. Coulie, and T. Boon. 2004. J. Exp. Med. 201:249-257).
在用MAGE抗原对黑色素瘤患者进行疫苗接种后，我们观察到，即使在少数出现肿瘤消退的患者中，血液中抗疫苗T细胞的频率通常也检测不到或低于CD8 T细胞的10^(-5)。这个频率可能太低，以至于这些细胞无法成为唯一的排斥效应细胞，因此我们重新审视了识别其他肿瘤抗原的T细胞的作用。黑色素瘤患者中存在此类抗肿瘤T细胞已被广泛报道。为了开始评估它们对疫苗诱导的排斥反应的作用，我们在5名接种疫苗的患者中评估了它们在血液中的频率。抗肿瘤细胞毒性T淋巴细胞（CTL）前体的频率范围为10^(-4)至3×10^(-3)，比同一患者体内的抗疫苗CTL高10到10000倍。在接种疫苗前也观察到了高频率。在一名用MAGE-3抗原接种疫苗后出现几乎完全消退的患者中，我们观察到了显著集中的抗肿瘤反应。大多数CTL前体（CTLp）识别由另一种癌胚基因MAGE-C2编码的抗原。其他的识别gp100抗原。识别MAGE-C2和gp100抗原的CTLp在接种疫苗前就已存在，但之后出现了新的克隆型。这些结果表明，一种已变得无效的自发抗肿瘤T细胞反应可以通过疫苗接种重新唤醒，并有助于肿瘤排斥。Lurquin等人（Lurquin, C., B. Lethe, V. Corbiere, I. Theate, N. van Baren, P.G. Coulie, and T. Boon. 2004. J. Exp. Med. 201:249-257）所展示的转移灶内观察到的抗疫苗和抗肿瘤CTL的频率进一步强化了这一观点。
