Photodynamic therapy enhancement of antitumor immunity is regulated by Neutrophils
Photodynamic therapy enhancement of antitumor immunity is regulated by Neutrophils
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DOI：
10.1158/0008-5472.can-07-1778
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发表时间：
2007-11-01
期刊：
影响因子：
11.2
通讯作者：
Gollnick, Sandra O.
中科院分区：
文献类型：
--
作者：
Kousis, Phiaretos C.;Henderson, Barbara W.;Gollnick, Sandra O.
光动力疗法（PDT）是美国食品和药物管理局批准的局部癌症治疗，可以治愈早期疾病和姑息晚期疾病。小鼠肿瘤的PDT导致方案依赖性诱导急性局部炎症反应，其部分特征是中性粒细胞快速浸润到治疗的肿瘤床中。在这项研究中，我们表明，PDT方案，诱导高水平的嗜中性粒细胞浸润产生肿瘤特异性的主要和记忆CD 8（+）T细胞反应。相比之下，从用PDT方案处理的小鼠中分离的免疫细胞（其诱导很少或不诱导嗜中性粒细胞浸润）表现出最小的抗肿瘤免疫。嗜中性粒细胞归巢到外周组织缺陷的小鼠（CXCR 2（-）/（-）小鼠）或嗜中性粒细胞耗尽的小鼠在PDT后不能产生强的抗肿瘤CD 8（+）T细胞应答。中性粒细胞似乎直接影响T细胞增殖和/或存活，而不是树突状细胞成熟或T细胞迁移。这些新的发现表明，通过增强T细胞增殖和/或存活，肿瘤浸润性中性粒细胞在PDT后建立抗肿瘤免疫中发挥重要作用。此外，我们的研究结果可能表明，中性粒细胞可能会影响其他炎症诱导癌症治疗后的抗肿瘤免疫的机制。我们的研究结果为合理设计PDT方案奠定了基础，这些方案可以在临床环境中最佳地增强抗肿瘤免疫力。免疫增强PDT方案然后可以与导致原发性肿瘤的最佳消融的治疗组合，从而抑制原发性肿瘤的生长并控制播散性疾病。
Photodynamic therapy (PDT) is a Food and Drug Administration-approved local cancer treatment that can be curative of early disease and palliative in advanced disease. PDT of murine tumors results in regimen-dependent induction of an acute local inflammatory reaction, characterized in part by rapid neutrophil infiltration into the treated tumor bed. In this study, we show that a PDT regimen that induced a high level of neutrophilic infiltrate generated tumor-specific primary and memory CD8(+) T-cell responses. In contrast, immune cells isolated from mice treated with a PDT regimen that induced little or no neutrophilic infiltrate exhibited minimal antitumor immunity. Mice defective in neutrophil homing to peripheral tissues (CXCR2(-)/(-) mice) or mice depleted of neutrophils were unable to mount strong antitumor CD8(+) T-cell responses following PDT. Neutrophils seemed to be directly affecting T-cell proliferation and/or survival rather than dendritic cell maturation or T-cell migration. These novel findings indicate that by augmenting T-cell proliferation and/or survival, tumor-infiltrating neutrophils play an essential role in establishment of antitumor immunity following PDT. Furthermore, our results may suggest a mechanism by which neutrophils might affect antitumor immunity following other inflammation-inducing cancer therapies. Our findings lay the foundation for the rational design of PDT regimens that lead to optimal enhancement of antitumor immunity in a clinical setting. Immune-enhancing PDT regimens may then be combined with treatments that result in optimal ablation of primary tumors, thus inhibiting growth of primary tumor and controlling disseminated disease.