Dissecting the impact of L-selectin on T lymphocyte dependent tumour immunity

剖析 L-选择素对 T 淋巴细胞依赖性肿瘤免疫的影响

• 批准号: MR/L008742/1
• 负责人: Ann Ager
• 金额: $ 55万
• 依托单位: CARDIFF UNIVERSITY
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2014
• 资助国家: 英国
• 起止时间: 2014 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FL008742%2F1
• 关键词: Dissecting; impact; selectin; lymphocyte; dependent

The harnessing of one's own immune system to treat a cancer, termed tumour immunotherapy, is an extremely attractive proposition because of the potential for combining high selectivity with low toxicity. Tumour immunotherapy has progressed significantly in recent years with improved understanding of how to boost the normally weak immune response to tumours. Nevertheless, there is considerable need for more improvements to ensure this form of treatment is more widely and effectively applied. Successful immunotherapy depends on immune cells, such as killer T lymphocytes, becoming activated and homing to the tumour. However, tumour blood vessels limit access of T lymphocytes to the tumour. We have found that T lymphocytes are better equipped to control tumour growth when they express the homing molecule L-selectin. We predict this is because L-selectin expression factilitates access of killer T cells to the tumour where they can deliver their lethal hit. The aim of this proposal is to study the properties of these L-selectin enhanced T lymphocytes and to determine whether they could be used to treat tumours. The potential long-term benefit of this work is that it will direct novel strategies for improving the clinical application of tumour immunotherapy.

利用自身的免疫系统来治疗癌症，称为肿瘤免疫疗法，是一个非常有吸引力的主张，因为它具有高选择性和低毒性相结合的潜力。近年来，随着对如何增强对肿瘤的通常较弱的免疫反应的理解的提高，肿瘤免疫治疗取得了显着进展。然而，仍有相当大的需要作出更多的改进，以确保这种治疗形式得到更广泛和更有效的应用。成功的免疫疗法取决于免疫细胞，如杀伤T淋巴细胞，被激活并归巢到肿瘤。然而，肿瘤血管限制T淋巴细胞进入肿瘤。我们发现，T淋巴细胞表达归巢分子L-选择素时，它们更有能力控制肿瘤生长。我们预测这是因为L-选择素的表达促进了杀伤性T细胞进入肿瘤，在那里它们可以提供致命的打击。该提案的目的是研究这些L-选择素增强的T淋巴细胞的特性，并确定它们是否可用于治疗肿瘤。这项工作的潜在长期益处是，它将指导改善肿瘤免疫治疗临床应用的新策略。

项目成果

Homing to solid cancers: a vascular checkpoint in adoptive cell therapy using CAR T-cells.

将固体癌的归巢：使用CAR T细胞疗法的血管检查点。

• DOI: 10.1042/bst20150254
• 发表时间: 2016-04-15
• 期刊: Biochemical Society transactions
• 影响因子: 3.9
• 作者: Ager A;Watson HA;Wehenkel SC;Mohammed RN
• 通讯作者: Mohammed RN

High Endothelial Venules and Other Blood Vessels: Critical Regulators of Lymphoid Organ Development and Function.

• DOI: 10.3389/fimmu.2017.00045
• 发表时间: 2017
• 期刊: Frontiers in immunology
• 影响因子: 7.3
• 作者: Ager A

Understanding high endothelial venules: Lessons for cancer immunology.

• DOI: 10.1080/2162402x.2015.1008791
• 发表时间: 2015-06
• 期刊: Oncoimmunology
• 影响因子: 7.2
• 作者: Ager A;May MJ
• 通讯作者: May MJ

Treg Depletion Licenses T Cell-Driven HEV Neogenesis and Promotes Tumor Destruction.

• DOI: 10.1158/2326-6066.cir-17-0131
• 发表时间: 2017-11
• 期刊: Cancer immunology research
• 影响因子: 10.1
• 作者: Colbeck EJ;Jones E;Hindley JP;Smart K;Schulz R;Browne M;Cutting S;Williams A;Parry L;Godkin A;Ware CF;Ager A;Gallimore A
• 通讯作者: Gallimore A

Cytokine regulation of lung Th17 response to airway immunization using LPS adjuvant.

• DOI: 10.1038/mi.2016.54
• 发表时间: 2017-03
• 期刊: Mucosal immunology
• 影响因子: 8