Mycobacteria activate γδ T-cell anti-tumour responses via cytokines from type 1 myeloid dendritic cells: a mechanism of action for cancer immunotherapy.
Mycobacteria activate γδ T-cell anti-tumour responses via cytokines from type 1 myeloid dendritic cells: a mechanism of action for cancer immunotherapy.
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DOI：
10.1007/s00262-011-1121-4
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发表时间：
2012-04
影响因子：
5.8
通讯作者：
Bodman-Smith, Mark D.
中科院分区：
文献类型：
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作者：
Fowler, Daniel W.;Copier, John;Wilson, Natalie;Dalgleish, Angus G.;Bodman-Smith, Mark D.
减毒和热杀分枝杆菌在临床表现出明显的抗癌活性；然而，诱导的免疫反应特征不明确，反应的潜在生物标志物也不明确。我们研究了目前临床上使用的三种分枝杆菌制剂（卡介苗、热杀母牛分枝杆菌和牛分枝杆菌）是否能刺激人γδ t细胞的抗肿瘤效应反应。通过测量细胞因子的产生、颗粒酶B的表达和对肿瘤靶细胞的细胞毒性来表征γδ t细胞的反应。结果表明，这些分枝杆菌制剂可激活γδ t细胞，激活标记物的表达和增殖均有所上调。活化的γδ t细胞表现出增强的效应反应，如颗粒酶B表达上调，TH1细胞因子IFN-γ和TNF-α的产生，以及对易感和唑来膦酸处理的耐药肿瘤细胞的脱颗粒反应增强。此外，IL-12、IL-1β和TNF-α可诱导循环中的1型髓样树突状细胞（DCs）的γδ t细胞活化，而2型髓样树突状细胞或浆细胞样树突状细胞则不能。综上所述，我们发现卡介苗、母牛分枝杆菌和奥巴马分枝杆菌通过循环dc的特定亚群间接诱导γδ t细胞抗肿瘤效应反应，并提出了卡介苗、母牛分枝杆菌和奥巴马分枝杆菌在癌症中潜在免疫治疗作用的机制。本文的在线版本（doi:10.1007/s00262-011-1121-4）包含补充材料，可供授权用户使用。
Attenuated and heat-killed mycobacteria display demonstrable activity against cancer in the clinic; however, the induced immune response is poorly characterised and potential biomarkers of response ill-defined. We investigated whether three mycobacterial preparations currently used in the clinic (BCG and heat-killed Mycobacterium vaccae and Mycobacterium obuense) can stimulate anti-tumour effector responses in human γδ T-cells. γδ T-cell responses were characterised by measuring cytokine production, expression of granzyme B and cytotoxicity against tumour target cells. Results show that γδ T-cells are activated by these mycobacterial preparations, as indicated by upregulation of activation marker expression and proliferation. Activated γδ T-cells display enhanced effector responses, as shown by upregulated granzyme B expression, production of the TH1 cytokines IFN-γ and TNF-α, and enhanced degranulation in response to susceptible and zoledronic acid-treated resistant tumour cells. Moreover, γδ T-cell activation is induced by IL-12, IL-1β and TNF-α from circulating type 1 myeloid dendritic cells (DCs), but not from type 2 myeloid DCs or plasmacytoid DCs. Taken together, we show that BCG, M. vaccae and M. obuense induce γδ T-cell anti-tumour effector responses indirectly via a specific subset of circulating DCs and suggest a mechanism for the potential immunotherapeutic effects of BCG, M. vaccae and M. obuense in cancer. The online version of this article (doi:10.1007/s00262-011-1121-4) contains supplementary material, which is available to authorized users.
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影响因子：
11.2
作者：
Dieli F;Vermijlen D;Fulfaro F;Caccamo N;Meraviglia S;Cicero G;Roberts A;Buccheri S;D'Asaro M;Gebbia N;Salerno A;Eberl M;Hayday AC
通讯作者：
Hayday AC
影响因子：
50.5
作者：
O'Brien, MER;Anderson, H;Reck, M
通讯作者：
Reck, M
影响因子：
6.6
作者：
Herr, Harry W.;Moralest, Alvaro
通讯作者：
Moralest, Alvaro
影响因子：
5.8
作者：
Mattarollo, Stephen R.;Kenna, Tony;Nicol, Andrew J.
通讯作者：
Nicol, Andrew J.
DOI：
10.1158/1078-0432.ccr-07-4912
发表时间：
2008-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Alexander AA;Maniar A;Cummings JS;Hebbeler AM;Schulze DH;Gastman BR;Pauza CD;Strome SE;Chapoval AI
通讯作者：
Chapoval AI