Chaux P, Favre N, Martin M, Martin F
Department of Biology and Therapy of Cancer, Faculty of Medicine, Dijon, France.
Int J Cancer. 1997 Aug 7;72(4):619-24. doi: 10.1002/(sici)1097-0215(19970807)72:4<619::aid-ijc12>3.0.co;2-6.
Tumors are tolerated by the immune system notwithstanding the expression of tumor-associated antigens. PROb tumor cells, derived from a rat colon carcinoma, are rejected by tumor-immune hosts but give rise to progressive tumors in naive hosts. Paradoxically, these tumors are heavily infiltrated by dendritic cells that express MHC class II and ICAM-1. These tumor-infiltrating dendritic cells (TiDCs) could be expected to process and present to T cells the antigens released by the adjacent tumor cells. Indeed, we report here that TiDCs, compared with splenic dendritic cells, are poor stimulators of primary allogeneic T-cell proliferation and cytokine [interleukin-2 (IL-2) and interferon-gamma] production. Most of them (89-97%) do not express B7, an essential co-stimulatory signal for T cells, even after a culture period allowing B7 up-regulation on epidermal Langerhans cells. GM-CSF in association with tumor necrosis factor-alpha or IL-4, or cell-associated CD40-ligand, all known to be potent stimulators of B7 expression on other dendritic cells, did not restore B7 expression by TiDCs. After a first exposure to TiDCs, allogeneic T-cell response to a second challenge to splenic dendritic cells was decreased. The failure of most dendritic cells infiltrating PROb tumors to express B7, even after stimulation, may contribute to their poor capacity to stimulate T cells and could play a role in the immune tolerance allowing tumor growth.
尽管肿瘤表达肿瘤相关抗原，但仍能被免疫系统所耐受。源自大鼠结肠癌的PROb肿瘤细胞可被肿瘤免疫宿主排斥，但在未致敏宿主中会引发进行性肿瘤。矛盾的是，这些肿瘤被表达MHC II类分子和细胞间黏附分子-1的树突状细胞大量浸润。这些肿瘤浸润性树突状细胞（TiDCs）有望处理并将相邻肿瘤细胞释放的抗原呈递给T细胞。事实上，我们在此报告，与脾树突状细胞相比，TiDCs对原发性同种异体T细胞增殖和细胞因子[白细胞介素-2（IL-2）和干扰素-γ]产生的刺激作用较弱。即使在经过一段能使表皮朗格汉斯细胞上调B7的培养期后，它们中的大多数（89 - 97%）仍不表达B7，而B7是T细胞必不可少的共刺激信号。已知与肿瘤坏死因子-α或IL-4联合的粒细胞-巨噬细胞集落刺激因子（GM-CSF），或细胞相关的CD40配体，都是其他树突状细胞上B7表达的有效刺激物，但它们并不能恢复TiDCs的B7表达。在首次接触TiDCs后，同种异体T细胞对再次接触脾树突状细胞的反应会降低。即使在受到刺激后，大多数浸润PROb肿瘤的树突状细胞仍无法表达B7，这可能导致它们刺激T细胞的能力较差，并可能在允许肿瘤生长的免疫耐受中发挥作用。
