Bonnotte B, Favre N, Moutet M, Fromentin A, Solary E, Martin M, Martin F
Department of Biology, Institut National de la Santé et de la Recherche Médicale U 517, Faculty of Medicine and Pharmacy, Dijon, France.
J Immunol. 2000 Feb 15;164(4):1995-2000. doi: 10.4049/jimmunol.164.4.1995.
Establishment of an immune response against cancer may depend on the capacity of dendritic cells to transfer tumor Ags into T cell-rich areas. To check this possibility, we used a colon cancer cell variant that yields tumors undergoing complete T cell-dependent rejection when injected into syngeneic rats. We previously demonstrated that immunogenicity of these tumors depended on the early apoptosis of a part of these tumor cells. In this paper we show that fluorescent tumor cell proteins are released from FITC-labeled tumor cells and undergo engulfment by tumor-infiltrating monocytes without a phenotype of mature dendritic cells or macrophages. Fluorescence-labeled mononuclear cells with a phenotype of MHC class II+ dendritic cells are also found in the T cell areas of the draining lymph nodes. Interestingly, no fluorescent cell can be found in lymph nodes after a s.c. injection of Bcl2-transfected apoptosis-resistant tumor cells that yielded progressive tumors. Proliferation of tumor-immune T lymphocytes was induced by dendritic cells isolated from the draining lymph nodes recovered after a s.c. injection of apoptosis-sensitive, but not apoptosis-resistant, tumor cells. These results show that tumor cell apoptosis releases proteins that are engulfed by inflammatory cells in the tumor, then transported to lymph node T cell areas where they can induce a specific immune response leading to tumor rejection.
针对癌症建立免疫反应可能取决于树突状细胞将肿瘤抗原转移至富含T细胞区域的能力。为验证这种可能性，我们使用了一种结肠癌细胞变体，将其注射到同基因大鼠体内时会引发完全依赖T细胞的肿瘤排斥反应。我们之前证明这些肿瘤的免疫原性取决于部分肿瘤细胞的早期凋亡。在本文中，我们表明荧光肿瘤细胞蛋白从FITC标记的肿瘤细胞中释放出来，并被肿瘤浸润的单核细胞吞噬，这些单核细胞没有成熟树突状细胞或巨噬细胞的表型。在引流淋巴结的T细胞区域也发现了具有II类MHC+树突状细胞表型的荧光标记单核细胞。有趣的是，皮下注射产生进行性肿瘤的Bcl2转染的抗凋亡肿瘤细胞后，在淋巴结中未发现荧光细胞。皮下注射凋亡敏感而非抗凋亡的肿瘤细胞后，从回收的引流淋巴结中分离出的树突状细胞可诱导肿瘤免疫T淋巴细胞增殖。这些结果表明，肿瘤细胞凋亡释放的蛋白被肿瘤中的炎性细胞吞噬，然后转运至淋巴结T细胞区域，在那里它们可诱导导致肿瘤排斥的特异性免疫反应。
