T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?
T-cell mediated anti-tumor immunity after photodynamic therapy: why does it not always work and how can we improve it?
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DOI：
10.1039/c4pp00455h
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Hamblin MR
中科院分区：
文献类型：
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作者：
Anzengruber F;Avci P;de Freitas LF;Hamblin MR
光动力疗法（PDT）使用无毒光敏剂和无害光的组合来产生活性氧物质，其通过直接杀死肿瘤细胞、血管关闭和激活免疫系统的组合来破坏肿瘤。在一些动物模型中已经显示，已经通过PDT治愈癌症的小鼠可能表现出对再激发的抗性。治愈的小鼠还可以拥有识别特定肿瘤抗原的肿瘤特异性T细胞，在体外破坏肿瘤细胞，并可以过继转移以保护未治疗的小鼠免受癌症的侵害。然而，这些有益的结果是例外，而不是规则。这种缺乏一致性的原因在于许多肿瘤抑制宿主免疫系统并主动逃避免疫攻击的能力。在特定肿瘤细胞系中存在适当的肿瘤排斥抗原是T细胞介导的免疫的必要条件。调节性T细胞（CD25+、Foxp3+）是抗肿瘤免疫的有效抑制剂，并且通过低剂量环磷酰胺去除它们可以增强PDT诱导的免疫应答。刺激树突状细胞（DC）的治疗，如CpG寡核苷酸，可以克服肿瘤诱导的DC功能障碍，改善PDT的结果。表观遗传逆转剂可以增加肿瘤I类MHC的表达，同时也增加肿瘤抗原的表达。一些临床报告表明，PDT可以在患者中产生抗肿瘤免疫，并且希望这些组合方法可以提高患者的肿瘤治愈率。抗肿瘤PDT释放抗原，这些抗原被迁移到淋巴结的树突状细胞吸收，引发增殖并返回以破坏剩余肿瘤细胞的幼稚T细胞。
Photodynamic therapy (PDT) uses the combination of non-toxic photosensitizers and harmless light to generate reactive oxygen species that destroy tumors by a combination of direct tumor cell killing, vascular shutdown, and activation of the immune system. It has been shown in some animal models that mice that have been cured of cancer by PDT, may exhibit resistance to rechallenge. The cured mice can also possess tumor specific T-cells that recognize defined tumor antigens, destroy tumor cells in vitro, and can be adoptively transferred to protect naïve mice from cancer. However, these beneficial outcomes are the exception rather than the rule. The reasons for this lack of consistency lie in the ability of many tumors to suppress the host immune system and to actively evade immune attack. The presence of an appropriate tumor rejection antigen in the particular tumor cell line is a requisite for T-cell mediated immunity. Regulatory T-cells (CD25+, Foxp3+) are potent inhibitors of anti-tumor immunity, and their removal by low dose cyclophosphamide can potentiate the PDT-induced immune response. Treatments that stimulate dendritic cells (DC) such as CpG oligonucleotide can overcome tumor-induced DC dysfunction and improve PDT outcome. Epigenetic reversal agents can increase tumor expression of MHC class I and also simultaneously increase expression of tumor antigens. A few clinical reports have shown that anti-tumor immunity can be generated by PDT in patients, and it is hoped that these combination approaches may increase tumor cures in patients. Anti-tumor PDT liberates antigens that are taken up by dendritic cells that migrate to lymph nodes, prime naïve T-cells that proliferate and return to destroy remaining tumor cells.