H2020Индивидуална стипендия2021–2023

ECONOMY · Endothelial Cells - an Overlooked Non-hematopoietic cOmponent of tuMor immunitY

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

Период: 2021-08-01 → 2023-07-31
Финансиране от ЕС: 166 320 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Ендотелните клетки, които облицоват кръвоносните съдове, се изследват за това как влияят на имунните клетки при рак на белия дроб. Разбирането на тези взаимодействия помага за подобряване на имунотерапията при пациенти, които проявяват резистентност към лечението.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Endothelial Cells - an Overlooked Non-hematopoietic cOmponent of tuMor immunitY

In this study, we analyzed the interactions of endothelial cells with immune cells in the context of lung cancer. Immune cells are the body’s natural defense against harmful substances and microorganisms, as well as abnormal tumor cells arising in the body. However, their ability to fight tumor cells is often hampered by interactions with other cell types and factors secreted to the environment around the tumor that can render these immune cells inert. Many cancer therapies are designed to re-activate the immune cells, and thereby activate the body’s own defense mechanism against the tumor (so-called immunotherapies). Although such treatments have proven successful in some cancer patients, these therapies often encounter resistance in the majority of cases. Furthermore, in cases of intital treatment success, patients often relapse later on. To improve these therapies, it is necessary to gain a better understanding of how immune cells are impacted by the cells surrounding them. Endothelial cells are the cells that line the inner walls of blood vessels, and therefore function as a barrier between the tumor and the blood stream, where the immune cells are recruited from. Thus, immune cells have to pass through the endothelial cell layer to reach the tumor. Potential interactions between endothelial cells and immune cells could therefore be very significant, as they may change the characteristics of immune cells before they encounter the tumor cells. Very interestingly, it has been observed that endothelial cells express proteins that are known to modulate the immune system (so-called immunoregulatory proteins). This was surprising, because such molecules are usually only found on different types of immune cells, or on cancer cells. However, it remains unknown if endothelial cells could interact with immune cells via these proteins. In our study, we investigated the role of endothelial cells expressing immunoregulatory proteins in tumors. We studied their interactions with immune cells, and examined how those impacted tumor growth and the response to immunotherapy. Using animal models of lung cancer, we identified a potential biomarker that may predict the response of the tumor to immunotherapy (see below). Currently our results are validated in clinical samples. Our results will ultimately (a) help to better identify the patients most likely to respond to immunotherapy, and (b) lead to future work involving modulating the tumor immunity by altering the endothelial barrier to enhance the efficacy of immunotherapies.

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

Цел на проекта

Despite decades of research, cancer remains the second leading cause of death globally. Amongst all cancers, lung cancer is the deadliest in both men and women worldwide. Immune checkpoint blockade (ICB) recently emerged as promising cancer therapy. While extremely successful in hematopoietic cancers and melanoma, success in lung cancer is very limited. We are therefore in desperate need to devise novel treatment strategies. One approach would involve remodelling the lung cancer immune landscape to improve clinical response to ICB. A so far overlooked non-hematopoietic component of the immune system which potentially greatly contribute to tumor immunity are endothelial cells (ECs). Most intriguingly, tumor EC (TEC) subsets expressing diverse immune markers were identified, in parallel with the discovery of diverse metabolic phenotypes in TECs. The host lab identified TECs with transcriptional signatures related to antigen processing and presentation (MHCII+). However, the functional significance of MHCII+ TECs in tumor immunity and whether their immune-related functions could be regulated by underlying metabolic programming is unknown. Given the strategic ""first line"" location of TECs in the tissue, the question is whether, ICB’s effectiveness can be partly attributed to TEC immunity. I therefore propose to investigate the interactions between MHCII+ TECs and T cells and the effects of such interactions on tumor immunity using state-of-the-art inducible EC-specific MHCII knock-out mice. Moreover, I will assess metabolic signatures in immune-TECs and test potential metabolic regulation of TECs’ immune functions. Such metabolism-driven regulation could open new therapeutic possibilities, utilizing already available pharmaceutical inhibitors to remodel the tumor immune landscape in order to create a favourable context for immunotherapy. Thus, the proposed research is expected to pave the way for exciting new combination treatment strategies for lung cancer.""

Оригинален текст от CORDIS (на английски).

Участници

VIB VZW · ZWIJNAARDE - GENTКоординаторБелгия