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肿瘤细胞上的B7-2表达对于低剂量美法仑治疗的MOPC-315荷瘤小鼠脾脏细胞获得细胞毒性T淋巴细胞活性很重要,其机制要求宿主抗原呈递细胞上表达B7-1或B7-2。

B7-2 expression on tumor cells is important for the acquisition of cytotoxic T lymphocyte activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers via a mechanism that requires either B7-1 or B7-2 expression on host antigen-presenting cells.

作者信息

Sojka D K, La Motte R N, Mokyr M B

机构信息

Department of Biochemistry and Molecular Biology, University of Illinois at Chicago, 60612, USA.

出版信息

Cancer Immunol Immunother. 2000 Apr;49(1):10-22. doi: 10.1007/s002620050022.

DOI:10.1007/s002620050022
PMID:10782862
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11036950/
Abstract

We have previously shown that B7-2 (CD86) and, to a lesser extent, B7-1 (CD80) contribute to the curative effectiveness of low-dose melphalan (L-phenylalanine mustard) for mice bearing a large MOPC-315 tumor under conditions that lead to the acquisition of potent cytotoxic T lymphocyte (CTL) activity at the tumor site. Since B7-1 and B7-2 are expressed on both tumor cells and host antigen-presenting cells (APC), the current studies were undertaken to examine the relative importance of each costimulatory molecule on tumor cells and on host APC for the acquisition of anti-MOPC-315 CTL activity. Utilizing an in vitro system for the acquisition of CTL activity, we found that B7 expression on host APC is important for the development of CTL activity in stimulation cultures of spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers, although the expression of either B7-1 or B7-2 is sufficient. In addition, we found that B7-2, which is expressed at high levels on stimulator tumor cells, but not B7-1, which is expressed at much lower levels, is also important for the acquisition of CTL activity. However, the vast majority of the CTL activity acquired in vitro in response to stimulation with the B7-2-expressing MOPC-315 tumor cells was found to depend on B7-expressing host APC. Thus, it is likely that B7-2, which is expressed at high levels on MOPC-315 tumor cells, promotes the rapid lysis of MOPC-315 stimulator tumor cells, thereby making tumor-associated antigens more readily available for efficient presentation by B7-expressing host APC which, in turn, stimulate the acquisition of CTL activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers.

摘要

我们之前已经表明,B7-2(CD86)以及在较小程度上的B7-1(CD80),在导致肿瘤部位获得强效细胞毒性T淋巴细胞(CTL)活性的条件下,对携带大的MOPC-315肿瘤的小鼠使用低剂量美法仑(L-苯丙氨酸氮芥)的治疗效果有贡献。由于B7-1和B7-2在肿瘤细胞和宿主抗原呈递细胞(APC)上均有表达,因此进行了当前研究,以检查每种共刺激分子在肿瘤细胞和宿主APC上对于获得抗MOPC-315 CTL活性的相对重要性。利用体外获得CTL活性的系统,我们发现宿主APC上的B7表达对于低剂量美法仑治疗的MOPC-315肿瘤携带者脾细胞刺激培养物中CTL活性的发展很重要,尽管B7-1或B7-2的表达就足够了。此外,我们发现,在刺激肿瘤细胞上高水平表达的B7-2,而不是表达水平低得多的B7-1,对于获得CTL活性也很重要。然而,发现体外响应表达B7-2的MOPC-315肿瘤细胞刺激而获得的绝大多数CTL活性依赖于表达B7的宿主APC。因此,很可能在MOPC-315肿瘤细胞上高水平表达的B7-2促进了MOPC-315刺激肿瘤细胞的快速裂解,从而使肿瘤相关抗原更易于被表达B7的宿主APC有效呈递,进而刺激来自低剂量美法仑治疗的MOPC-315肿瘤携带者脾细胞获得CTL活性。

相似文献

1
B7-2 expression on tumor cells is important for the acquisition of cytotoxic T lymphocyte activity by spleen cells from low-dose-melphalan-treated MOPC-315 tumor bearers via a mechanism that requires either B7-1 or B7-2 expression on host antigen-presenting cells.肿瘤细胞上的B7-2表达对于低剂量美法仑治疗的MOPC-315荷瘤小鼠脾脏细胞获得细胞毒性T淋巴细胞活性很重要,其机制要求宿主抗原呈递细胞上表达B7-1或B7-2。
Cancer Immunol Immunother. 2000 Apr;49(1):10-22. doi: 10.1007/s002620050022.
2
Importance of the B7-2 molecule for low dose melphalan-induced acquisition of tumor-eradicating immunity by mice bearing a large MOPC-315 tumor.B7-2分子对携带大剂量MOPC-315肿瘤的小鼠经低剂量美法仑诱导获得肿瘤根除免疫的重要性。
J Immunol. 1998 Feb 15;160(4):1866-74.
3
Limited importance of CD40/CD40L interaction in the B7-dependent generation of anti-MOPC-315 cytotoxic T lymphocyte activity by tumor bearer splenic cells stimulated in vitro in the presence of tumor necrosis factor.在肿瘤坏死因子存在的情况下体外刺激荷瘤小鼠脾细胞时,CD40/CD40L相互作用在依赖B7产生抗MOPC - 315细胞毒性T淋巴细胞活性方面的重要性有限。
Cancer Immunol Immunother. 1998 Aug;46(6):293-303. doi: 10.1007/s002620050490.
4
Transforming growth factor-beta-mediated down-regulation of antitumor cytotoxicity of spleen cells from MOPC-315 tumor-bearing mice engaged in tumor eradication following low-dose melphalan therapy.转化生长因子-β介导荷MOPC-315肿瘤小鼠脾细胞抗肿瘤细胞毒性的下调,这些脾细胞在小剂量美法仑治疗后参与肿瘤清除。
Cancer Immunol Immunother. 1994 Apr;38(4):215-24. doi: 10.1007/BF01533512.
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Low-dose-melphalan-induced up-regulation of type-1 cytokine expression in the s.c. tumor nodule of MOPC-315 tumor bearers and the role of interferon gamma in the therapeutic outcome.低剂量美法仑诱导MOPC - 315荷瘤小鼠皮下肿瘤结节中1型细胞因子表达上调及干扰素γ在治疗结果中的作用
Cancer Immunol Immunother. 1995 Dec;41(6):363-74. doi: 10.1007/BF01526556.
6
Melphalan and other anticancer modalities up-regulate B7-1 gene expression in tumor cells.美法仑和其他抗癌方式可上调肿瘤细胞中B7-1基因的表达。
J Immunol. 2000 Jun 15;164(12):6230-6. doi: 10.4049/jimmunol.164.12.6230.
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Importance of TNF production for the curative effectiveness of low dose melphalan therapy for mice bearing a large MOPC-315 tumor.肿瘤坏死因子(TNF)产生对低剂量美法仑治疗携带大MOPC - 315肿瘤小鼠疗效的重要性。
J Immunol. 1995 Apr 15;154(8):3941-51.
8
Lysis of antigenically unrelated tumor cells mediated by Lyt 2+ splenic T-cells from melphalan-cured MOPC-315 tumor bearers.来自美法仑治愈的MOPC - 315肿瘤荷瘤小鼠的Lyt 2 + 脾T细胞介导的与抗原无关的肿瘤细胞溶解作用。
Cancer Res. 1989 Sep 15;49(18):5007-15.
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Low-dose melphalan-induced shift in the production of a Th2-type cytokine to a Th1-type cytokine in mice bearing a large MOPC-315 tumor.低剂量美法仑诱导携带大型MOPC - 315肿瘤的小鼠体内Th2型细胞因子产生向Th1型细胞因子的转变。
Cancer Immunol Immunother. 1994 Aug;39(2):117-26. doi: 10.1007/BF01525317.
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Specificity of the generation and expression of enhanced anti-plasmacytoma immunity by spleen cells from melphalan-treated MOPC-315 tumor bearers.美法仑处理的MOPC - 315荷瘤小鼠脾脏细胞产生和表达增强的抗浆细胞瘤免疫的特异性
Cancer Immunol Immunother. 1986;23(1):11-9. doi: 10.1007/BF00205549.

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