Elimination of metastatic melanoma using gold nanoshell-enabled photothermal therapy and adoptive T cell transfer.
Elimination of metastatic melanoma using gold nanoshell-enabled photothermal therapy and adoptive T cell transfer.
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DOI：
10.1371/journal.pone.0069073
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Foster AE
中科院分区：
文献类型：
--
作者：
Bear AS;Kennedy LC;Young JK;Perna SK;Mattos Almeida JP;Lin AY;Eckels PC;Drezek RA;Foster AE
诸如光热疗法（PTT）的消融治疗是有吸引力的抗癌策略，因为它们使可接近的肿瘤部位减容，同时引发抗肿瘤免疫应答。然而，热消融后的免疫应答通常不足以治疗转移性疾病。在这里，我们证明，PTT诱导促炎细胞因子和趋化因子的表达，并促进肿瘤引流淋巴结内的树突状细胞的成熟，从而引发抗肿瘤T细胞反应。然而，出乎意料的是，这些免疫调节作用对总体抗肿瘤免疫力无益。我们发现，PTT促进了CD 11b +Ly-6 G/C+骨髓源性抑制细胞对继发性肿瘤部位的浸润，因此未能减缓免疫原性差的B16-F10肿瘤的生长，并增强了远处肺转移的生长。为了利用PTT活性对局部肿瘤和抗肿瘤免疫的有益作用，同时避免不良后果，我们在PTT后过继转移gp 100特异性pmel T细胞。PTT的局部控制和过继转移的T细胞提供的全身抗肿瘤免疫反应性的组合预防了消融后的原发性肿瘤复发，抑制了远端部位的肿瘤生长，并消除了肺转移瘤的生长。因此，PTT和全身免疫疗法的组合预防了PTT对转移性肿瘤生长的不良作用，并优化了总体肿瘤控制。
Ablative treatments such as photothermal therapy (PTT) are attractive anticancer strategies because they debulk accessible tumor sites while simultaneously priming antitumor immune responses. However, the immune response following thermal ablation is often insufficient to treat metastatic disease. Here we demonstrate that PTT induces the expression of proinflammatory cytokines and chemokines and promotes the maturation of dendritic cells within tumor-draining lymph nodes, thereby priming antitumor T cell responses. Unexpectedly, however, these immunomodulatory effects were not beneficial to overall antitumor immunity. We found that PTT promoted the infiltration of secondary tumor sites by CD11b+Ly-6G/C+ myeloid-derived suppressor cells, consequently failing to slow the growth of poorly immunogenic B16-F10 tumors and enhancing the growth of distant lung metastases. To exploit the beneficial effects of PTT activity against local tumors and on antitumor immunity whilst avoiding the adverse consequences, we adoptively transferred gp100-specific pmel T cells following PTT. The combination of local control by PTT and systemic antitumor immune reactivity provided by adoptively transferred T cells prevented primary tumor recurrence post-ablation, inhibited tumor growth at distant sites, and abrogated the outgrowth of lung metastases. Hence, the combination of PTT and systemic immunotherapy prevented the adverse effects of PTT on metastatic tumor growth and optimized overall tumor control.
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影响因子：
11.2
作者：
Harlin H;Meng Y;Peterson AC;Zha Y;Tretiakova M;Slingluff C;McKee M;Gajewski TF
通讯作者：
Gajewski TF
影响因子：
3.8
作者：
Finnerty, Celeste C.;Przkora, Rene;Herndon, David N.;Jeschke, Marc G.
通讯作者：
Jeschke, Marc G.
影响因子：
11.5
作者：
Gajewski, Thomas F.
通讯作者：
Gajewski, Thomas F.
DOI：
10.1073/pnas.2232479100
发表时间：
2003-11-11
影响因子：
11.1
作者：
Hirsch, LR;Stafford, RJ;West, JL
通讯作者：
West, JL
影响因子：
20.3
作者：
Menetrier-Caux, C;Montmain, G;Blay, JY
通讯作者：
Blay, JY