PanILC · Deciphering type 2 innate lymphoid cell/epithelial progenitor cell crosstalk in pancreas regeneration and neoplasia
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-07-01 → 2021-06-30
- Финансиране от ЕС
- 224 934 €
- Участници
- 1
- Схема
- MSCA-IF-EF-ST
Линиите свързват координатора с партньорите.
Накратко на български
Имунните клетки от тип ILC2 и тяхното взаимодействие с епителните клетки в панкреаса се анализират чрез миша модели на възпаление и тумори. Разбирането на тези процеси е важно, защото ракът на панкреаса е агресивен и остава устойчив на съвременните имунотерапии.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Deciphering type 2 innate lymphoid cell/epithelial progenitor cell crosstalk in pancreas regeneration and neoplasia
Over the last decade, treatment of cancer has been revolutionised by the tremendous success of cancer immunotherapies, i.e. drugs aiming at boosting the patient’s own immune system against its tumour. Such treatments have led to improved survival and long-term remission in a substantial proportion of treated patients, and have now become the standard of care in specific tumour types, such as melanoma. However, not all types of tumours are sensitive to immunotherapies. One such example is pancreatic cancer, among which pancreatic adenocarcinoma (PDAC) represents the most common subtype. PDAC is one of the most aggressive cancer types, with a five-year survival rate of less than 5%. Among PDAC risk factors, pancreatitis emerges as a critical player in tumour development, as evidenced from both human data and pre-clinical mouse models. Despite intensive research, no improvement in this five-year survival rate has been achieved over the past 4 decades, illustrating how cutting-edge research in this field is crucial to tackle such an unmet clinical need. An extensive amount of work has been achieved at defining critical signalling pathways for pancreatic cancer cell survival as well as the mutational landscape in pancreatic tumours. However, our understanding of the interaction between immune cells and the exocrine pancreas – healthy, inflamed or tumoral – has just begun to be explored. In this work we set out to test the hypothesis that a novel subset of tissue-resident immune cells termed “type-2 innate lymphoid cells”, or ILC2s, influence the epithelial cell niche in the pancreas by locally regulating inflammation. Using state-of-the art mouse models of pancreatitis and pancreatic tumors, our results reveal distinct and previously unappreciated roles for ILC2s-driven mechanisms in regulating pancreatic epithelial cells upon inflammation and tumorigenesis.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Regulation of the epithelial stem cell compartment is critical for tissue homeostasis and regeneration. Consequently, imbalance in this process, through acquisition of somatic mutations for instance, may give rise to tumorigenesis. Emerging reports reveal that regulatory T cells (Tregs) can modulate epithelial stem cell dynamics in the skin, while type 2 innate lymphoid cells (ILC2s) are known to influence tissue-regeneration. Recent work in our laboratory has elucidated that ILC2s crosstalk is essential for local Tregs expansion. We hypothesize that tissue-resident ILC2s influence the stem cell niche by recruiting and regulating Tregs, and that such a mechanism could be key to tissue regeneration as well as tumor development.Preliminary data in the lab suggest that the intraperitoneal injection of the potent ILC2 inducer IL-33 in mice activates ILC2 in the pancreas, and that a concomitant increase in Treg numbers is observed in this organ. This raises the possibility of the existence of a crosstalk between ILC2s and Tregs in the pancreas upon inflammation, such as in the case of pancreatitis. Given the considerable attention brought lately on the ability of Tregs to develop tissue-promoting capacities, we postulate that regeneration of the exocrine pancreas following pancreatitis may be driven by such pancreatic Tregs upon their “priming” by ILC2.The present project will therefore focus on understanding the role of ILC2 and Tregs and their possible crosstalk in pancreatitis development, as well as in the regeneration process that follows, i.e. the interaction of these immune cells with epithelial progenitors. As pancreatitis is a major risk factor for the development of pancreatic cancer, the resulting observations will then be extended to the analysis of the role of ILC2/Treg crosstalk in tumor development in an orthotopic mouse model of pancreatic tumours as well as in a genetic mouse model of pancreatic adenocarcinoma.
Оригинален текст от CORDIS (на английски).
Участници
- THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE · CAMBRIDGEКоординаторОбединеното кралство
Връзки
Данни: CORDIS, © Европейски съюз