ICAM-1 contributes to but is not essential for tumor antigen cross-priming and CD8+ T cell-mediated tumor rejection in vivo
ICAM-1 contributes to but is not essential for tumor antigen cross-priming and CD8+ T cell-mediated tumor rejection in vivo
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DOI：
10.4049/jimmunol.174.6.3416
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发表时间：
2005-03-15
影响因子：
4.4
通讯作者：
Gajewski, TF
中科院分区：
文献类型：
--
作者：
Blank, C;Brown, I;Gajewski, TF
ICAM-1已被描述为在T细胞活化期间提供粘附和共刺激功能。在抗肿瘤免疫的背景下，ICAM-1/LFA-1相互作用在引流淋巴结中APC引发T细胞以及跨内皮迁移和肿瘤部位的肿瘤细胞识别的水平上可能是重要的。为了确定ICAM-1对体内肿瘤排斥的贡献，我们将2C TCR转基因/RAG 2（-/-）T细胞过继转移到TCR α（-/-）与ICAM（-/-）/TCR α（-/-）受体动物中。ICAM-1缺陷小鼠成功地排斥了表达由2C TCR识别的L-d的HTR. C肿瘤，尽管具有动力学延迟。由于HTR. C肿瘤细胞本身表达ICAM-1，因此使用缺乏ICAM-1表达的B16-F10黑素瘤细胞进行第二种模型。这些细胞被转导以表达在K-B背景下由2C TCR识别的SIYRYYGL肽，其在体内由H-2（B）小鼠中的APC交叉呈递。这些肿瘤也生长得更慢，但最终被大多数ICAM-1（-/-）/TCR α（-/-）受体排斥。通过ELISPOT评估，ICAM-1（-/-）小鼠中的延迟排斥与T细胞引发减少相关。相比之下，野生型和ICAM-1（-/-）宿主中T细胞渗透到肿瘤中的程度相当，而过继转移的致敏效应2C细胞在ICANI-1（-/-）受体中正常排斥。我们的研究结果表明，ICAM-1有助于但不是绝对需要的CD 8（+）T细胞介导的肿瘤排斥反应在体内，并占主导地位的抗肿瘤免疫应答的启动水平，而不是效应阶段的作用。
ICAM-1 has been described to provide both adhesion and costimulatory functions during T cell activation. In the setting of antitumor immunity, ICAM-1/LFA-1 interactions could be important at the level of T cell priming by APCs in draining lymph nodes as well as for transendothelial migration and tumor cell recognition at the tumor site. To determine the contribution of ICAM-1 to tumor rejection in vivo, we performed adoptive transfer of 2C TCR-transgenic/RAG2(-/-) T cells into TCRalpha(-/-) vs ICAM(-/-)/TCRalpha(-/-) recipient animals. ICAM-1-deficient mice successfully rejected HTR.C tumors expressing L-d recognized by the 2C TCR, albeit with a kinetic delay. Inasmuch as HTR.C tumor cells themselves express ICAM-1, a second model was pursued using B16-F10 melanoma cells that lack ICAM-1 expression. These cells were transduced to express the SIYRYYGL peptide recognized by the 2C TCR in the context of K-b, which is cross-presented by APCs in H-2(b) mice in vivo. These tumors also grew more slowly but were eventually rejected by the majority of ICAM-1(-/-)/TCRalpha(-/-) recipients. Delayed rejection in ICAM-1(-/-) mice was associated with diminished T cell priming as assessed by ELISPOT. In contrast, T cell penetration into the tumor was comparable in wild-type and ICAM-1(-/-) hosts, and adoptively transferred primed effector 2C cells rejected normally in ICANI-1(-/-) recipients. Our results suggest that ICAM-1 contributes to but is not absolutely required for CD8(+) T cell-mediated tumor rejection in vivo and dominantly acts at the level of priming rather than the effector phase of the antitumor immune response.