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树突状细胞捕获死亡的肿瘤细胞并呈递其抗原,以引发肿瘤特异性免疫反应。

Dendritic cells capture killed tumor cells and present their antigens to elicit tumor-specific immune responses.

作者信息

Nouri-Shirazi M, Banchereau J, Bell D, Burkeholder S, Kraus E T, Davoust J, Palucka K A

机构信息

Baylor Institute for Immunology Research, Dallas, TX 75204, USA.

出版信息

J Immunol. 2000 Oct 1;165(7):3797-803. doi: 10.4049/jimmunol.165.7.3797.

Abstract

Due to their capacity to induce primary immune responses, dendritic cells (DC) are attractive vectors for immunotherapy of cancer. Yet the targeting of tumor Ags to DC remains a challenge. Here we show that immature human monocyte-derived DC capture various killed tumor cells, including Jurkat T cell lymphoma, malignant melanoma, and prostate carcinoma. DC loaded with killed tumor cells induce MHC class I- and class II-restricted proliferation of autologous CD8+ and CD4+ T cells, demonstrating cross-presentation of tumor cell-derived Ags. Furthermore, tumor-loaded DC elicit expansion of CTL with cytotoxic activity against the tumor cells used for immunization. CTL elicited by DC loaded with the PC3 prostate carcinoma cell bodies kill another prostate carcinoma cell line, DU145, suggesting recognition of shared Ags. Finally, CTL elicited by DC loaded with killed LNCap prostate carcinoma cells, which express prostate specific Ag (PSA), are able to kill PSA peptide-pulsed T2 cells. This demonstrates that induced CTL activity is not only due to alloantigens, and that alloantigens do not prevent the activation of T cells specific for tumor-associated Ags. This approach opens the possibility of using allogeneic tumor cells as a source of tumor Ag for antitumor therapies.

摘要

由于树突状细胞(DC)具有诱导初始免疫应答的能力,因此它是癌症免疫治疗中极具吸引力的载体。然而,将肿瘤抗原靶向递送至DC仍然是一项挑战。在此我们表明,未成熟的人单核细胞衍生的DC能够捕获各种经灭活的肿瘤细胞,包括Jurkat T细胞淋巴瘤、恶性黑色素瘤和前列腺癌。负载有经灭活肿瘤细胞的DC可诱导自体CD8⁺和CD4⁺ T细胞的MHC I类和II类限制性增殖,这表明肿瘤细胞衍生的抗原可发生交叉呈递。此外,负载肿瘤的DC可引发具有针对用于免疫的肿瘤细胞的细胞毒性活性的细胞毒性T淋巴细胞(CTL)的扩增。由负载PC3前列腺癌细胞体的DC引发的CTL可杀死另一种前列腺癌细胞系DU145,这表明存在对共同抗原的识别。最后,由负载经灭活的表达前列腺特异性抗原(PSA)的LNCap前列腺癌细胞的DC引发的CTL能够杀死经PSA肽脉冲处理的T2细胞。这表明诱导的CTL活性不仅归因于同种异体抗原,并且同种异体抗原不会阻止针对肿瘤相关抗原的T细胞的激活。这种方法为使用同种异体肿瘤细胞作为抗肿瘤治疗的肿瘤抗原来源开辟了可能性。

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