H2020Индивидуална стипендия2015–2017

Tolltum · Role, regulation and targeting of nucleic acid-sensing TLRs within the tumour microenvironment

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2015-10-01 → 2017-09-30
Финансиране от ЕС: 195 455 €
Участници: 1
Схема: MSCA-IF-EF-ST

Линиите свързват координатора с партньорите.

Накратко на български

Механизмите, чрез които раковите клетки при рак на гърдата избягват засичането от имунната система, се анализират чрез човешки тумори и клетъчни линии. Разбирането на тези процеси помага за подобряване на ефективността на имунотерапията при метастази.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Role, regulation and targeting of nucleic acid-sensing TLRs within the tumour microenvironment

The early detection of tumour cells by the immune system is crucial for stalling carcinogenesis and for tumour regression. Immunotherapy is gaining momentum as a primary treatment option owing to its success in treating tumours of different origins. However, the mechanisms leading to failure of the immune system to control tumour formation in the absence of therapy are poorly understood and requires more attention. Insights into these mechanisms would provide therapeutic targets to enhance the efficacy of immunotherapy and boost the endogenous immune response. The primary goal of this study is to identify mechanisms by which tumour cells prevent the activation and function of the immune system thereby leading to an inefficient anti-tumour response. Breast cancer ranks as the first in cancer deaths and the primary cause of death is tumour metastasis. Studies in mice and humans have shown that metastatic tumour cells develop several evasion mechanisms that suppress their detection by the immune system. The present project aims to shed light on these suppressive mechanisms that would provide novel therapeutic targets to deal with metastatic disease. The overall objective of this project is to use primary human tumours and established metastatic cancer cell lines to study cellular and molecular interactions within the tumour microenvironment that suppress the immune response. Our main focus is on inflammation and the recruitment of key immune cells within the tumour both of which are crucial to induce an efficient immune response.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Inflammation is an integral part of carcinogenesis. Several different cells of myeloid, lymphoid and non-hematopoietic origin contribute to the strong link between cancer and inflammation and maintain a pro-tumoral environment. The complexity of this environment and the diversity of tumours lead to distinct responses during tumour immunotherapies. Nucleic acid-sensing (NAS) TLR ligands are an essential component of anti-tumour strategies to induce efficient tumour-specific adaptive immune responses. NAS TLRs can also detect nucleic acid released during tumour necrosis, thereby modulating the tumour microenvironment. Interestingly, NAS TLR signalling can induce cell death via apoptosis or induce pro-tumoral survival and proliferation of cancer cells. These opposing effects of NAS TLR ligands may be due to the differential response of distinct tumour-associated cells to TLR ligands. Indeed, the individual response of subsets of tumour-associated cells remains unclear, thus making it difficult to predict the outcome of tumour immunotherapies. Furthermore, the expression and regulation of NAS TLRs in tumour-associated cells remains unknown. Using ex vivo cultures from adenocarcinomas and melanomas, we will systematically analyze the expression of all NAS TLRs on sorted cells. Using cutting edge technologies, we will dissect the role of TLRs in modulating the tumour microenvironment, which will provide novel insights into our ability to modulate cellular inflammation in the tumour. This proposal has the potential not only to reveal novel aspects of NAS TLR regulation, but also to provide new targets for the modulation of the tumour stroma and the infiltrating cells during carcinogenesis.

Оригинален текст от CORDIS (на английски).

Участници

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordКоординаторОбединеното кралство