Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor
Local radiation therapy of B16 melanoma tumors increases the generation of tumor antigen-specific effector cells that traffic to the tumor
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DOI：
10.4049/jimmunol.174.12.7516
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发表时间：
2005-06-15
影响因子：
4.4
通讯作者：
Lord, EM
中科院分区：
文献类型：
--
作者：
Lugade, AA;Moran, JP;Lord, EM
肿瘤的免疫治疗因其潜在的特异性和有限的副作用而备受关注。通过为免疫细胞激活提供佐剂信号和炎症环境，这种方法的效果可能会得到改善。我们用单次(15GY)或分次(5X3GY)局部电离辐射治疗表达OVA的B16-F0肿瘤后，评估了小鼠的抗肿瘤免疫反应。与未受照射的小鼠相比，受照射的小鼠具有更强的细胞呈递肿瘤抗原的能力，以及在肿瘤引流淋巴结内多肽刺激下分泌干扰素-γ的特异性T细胞。与未照射的小鼠相比，肿瘤引流淋巴结中的免疫激活与CD45(+)细胞渗入单次剂量照射的肿瘤的数量增加有关。同样，受辐射的小鼠有更多的肿瘤浸润性淋巴细胞，它们分泌干扰素-伽马并裂解肿瘤细胞靶点。多肽特异性的干扰素-γ分别针对I类和II类MHC限制性OVA多肽OVA(257-264)和OVA(323-339)，以及内源性I类MHC限制性B16肿瘤多肽酪氨酸酶相关蛋白2(180-188)。过继转移研究表明，照射肿瘤内肿瘤抗原特异性免疫细胞数量的增加最有可能是由于这些细胞向肿瘤部位的运输增加。综上所述，这些结果表明，局部放射可以增加抗肿瘤免疫效应细胞的产生和它们向肿瘤部位的运输。
Immunotherapy of cancer is attractive because of its potential for specificity and limited side effects. The efficacy of this approach may be improved by providing adjuvant signals and an inflammatory environment for immune cell activation. We evaluated antitumor immune responses in mice after treatment of OVA-expressing B16-F0 tumors with single (15 Gy) or fractionated (5 X 3 Gy) doses of localized ionizing radiation. Irradiated mice had cells with greater capability to present tumor Ags and specific T cells that secreted IFN-gamma upon peptide stimulation within tumor-draining lymph nodes than nonirradiated mice. Immune activation in tumor-draining lymph nodes correlated with an increase in the number of CD45(+) cells infiltrating single dose irradiated tumors compared with nonirradiated mice. Similarly, irradiated mice had increased numbers of tumor-infiltrating lymphocytes that secreted IFN-gamma and lysed tumor cell targets. Peptide-specific IFN-gamma responses were directed against both the class I and class II MHC-restricted OVA peptides OVA(257-264) and OVA(323-339), respectively, as well as the endogenous class I MHC-restricted B16 tumor peptide tyrosinase-related protein 2(180-188). Adoptive transfer studies indicated that the increased numbers of tumor Ag-specific immune cells within irradiated tumors were most likely due to enhanced trafficking of these cells to the tumor site. Together these results suggest that localized radiation can increase both the generation of antitumor immune effector cells and their trafficking to the tumor site.