Role of MDA5 and interferon-I in dendritic cells for T cell expansion by anti-tumor peptide vaccines in mice.
Role of MDA5 and interferon-I in dendritic cells for T cell expansion by anti-tumor peptide vaccines in mice.
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DOI：
10.1007/s00262-018-2164-6
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发表时间：
2018-07
期刊：
影响因子：
--
通讯作者：
Celis E
中科院分区：
文献类型：
--
作者：
Sultan H;Wu J;Kumai T;Salazar AM;Celis E
细胞毒性T淋巴细胞（CTL）是能够破坏肿瘤细胞的免疫系统的有效组分。使用肽疫苗产生CTL是治疗癌症的实用方法。我们先前已经描述了肽疫苗接种策略，其在使用聚ICLC佐剂的2次连续免疫（初免-加强）后产生大量内源性肿瘤反应性CTL，所述聚ICLC佐剂刺激内体Toll样受体3（TLR 3）和细胞质黑素瘤分化抗原5（MDA 5）。树突状细胞（DC）不仅在抗原呈递中起重要作用，而且在产生促进CTL扩增的共刺激细胞因子中起关键作用。聚-ICLC显示出在各种DC亚群中产生I型干扰素（IFN-I）方面比聚-IC更有效，这是通过其增强的逃离内体隔室和刺激MDA 5的能力。在我们的系统中，IFN-I不直接作为T细胞共刺激细胞因子发挥作用，但通过诱导IL 15增强CTL扩增。对于棕榈酰化肽疫苗，CD 8a + DC对于肽交叉表达是必需的。对于疫苗加强，非专业抗原呈递细胞能够提出最小的表位肽，但DC仍然需要通过多聚ICLC介导的IFN-I的产生来进行CTL扩增。总之，这些结果阐明了DC、TLR 3、MDA 5、IFN-1和IL 15在使用肽和多聚IC疫苗产生大量有效的抗肿瘤CTL应答中的作用。DC上MDA 5的聚ICLC活化通过调节IFN-I和IL 15产生介导T细胞扩增。IFN-I不直接作为T细胞上的信号-3细胞因子起作用，但通过专业和非专业APC诱导IL 15的产生
Cytotoxic T lymphocytes (CTLs) are effective components of the immune system capable of destroying tumor cells. Generation of CTLs using peptide vaccines is a practical approach to treat cancer. We have previously described a peptide vaccination strategy that generates vast numbers of endogenous tumor-reactive CTLs after 2 sequential immunizations (prime-boost) using poly-ICLC adjuvant, which stimulates endosomal Toll-like receptor 3 (TLR3) and cytoplasmic melanoma differentiation antigen 5 (MDA5). Dendritic cells (DCs) play an important role not only in antigen presentation but are critical in generating costimulatory cytokines that promote CTL expansion. Poly-ICLC was shown to be more effective than poly-IC in generating type-I interferon (IFN-I) in various DC subsets, through its enhanced ability to escape endosomal compartment and stimulate MDA5. In our system IFN-I did not directly function as a T cell costimulatory cytokine, but enhanced CTL expansion through the induction of IL15. With palmitoylated peptide vaccines, CD8a+ DCs were essential for peptide crosspresentation. For vaccine boosts, nonprofessional antigen presenting cells were able to present minimal epitope peptides, but DCs were still required for CTL expansions through the production of IFN-I mediated by poly-ICLC. Overall, these results clarify the roles of DCs, TLR3, MDA5, IFN-I and IL15 in the generation of vast and effective antitumor CTL responses using peptide and poly-IC vaccines. Poly-ICLC activation of MDA5 on DCs mediates T cell expansion by regulating IFN-I and IL15 production. IFN-I does not directly function as a signal-3 cytokine on T cells but induces production of IL15 by professional and non-professional APCs
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影响因子：
32.4
作者：
Jung, S;Unutmaz, D;Lang, RA
通讯作者：
Lang, RA
DOI：
10.1084/jem.192.12.1685
发表时间：
2000-12-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
den Haan JM;Lehar SM;Bevan MJ
通讯作者：
Bevan MJ
DOI：
10.1089/jir.1981.1.539
发表时间：
1981-01-01
期刊：
JOURNAL OF INTERFERON RESEARCH
影响因子：
--
作者：
LAMPSON, GP;FIELD, AK;HILLEMAN, MR
通讯作者：
HILLEMAN, MR
影响因子：
4.4
作者：
Buhtoiarov, IN;Lum, H;Rakhmilevich, AL
通讯作者：
Rakhmilevich, AL
DOI：
10.1084/jem.20050821
发表时间：
2005-09-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kolumam GA;Thomas S;Thompson LJ;Sprent J;Murali-Krishna K
通讯作者：
Murali-Krishna K