H2020Индивидуална стипендия2022–2024

BreaKer · Dissecting how breast cancer-associated inflammation shapes invariant natural killer T cell activity during metastatic progression

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

Период: 2022-09-01 → 2024-12-21
Финансиране от ЕС: 175 572 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Възпалението при рака на гърдата и неговото влияние върху iNKT клетките, които атакуват туморите, са в центъра на анализа. Разбирането на този процес може да помогне за активиране на имунната система и подобряване на терапията 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

Dissecting how breast cancer-associated inflammation shapes invariant natural killer T cell activity during metastatic progression

Breast cancer is a major health challenge, and when it spreads to other parts of the body (metastatic breast cancer), it becomes much harder to treat. Despite medical advances, survival rates for metastatic breast cancer remain low. Immunotherapy, which uses the body's own immune system to fight cancer, has shown promise, but only a small number of patients benefit from it. This means we need a better understanding of how the immune system interacts with breast cancer, especially in its advanced stages. The immune system has different types of cells that work together to fight infections and diseases, including cancer. However, in cancer patients, this system often becomes unbalanced, allowing the disease to progress. One important type of immune cell, called invariant Natural Killer T (iNKT) cells, has the potential to fight tumors. These cells can quickly release substances that attack cancer and help other immune cells respond. However, iNKT cells do not always work effectively in breast cancer, and scientists do not yet fully understand why. Research suggests that changes in the environment around the tumor may weaken these cells, reducing their ability to fight the disease. This project aimed to investigate how inflammation associated with breast cancer affects iNKT cells and how these cells could be activated to improve cancer treatment.

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

Цел на проекта

Breast cancer is the second cause of cancer-related death in women. Although cancer immunotherapy emerged as a successful therapy for many cancer types, the response of metastatic breast cancer patients to immune checkpoint blockade remains disappointing, urging for a better understanding of the breast cancer immune landscape. iNKT cells are lipid-specific T cells that bridge innate and adaptive immunity and exert a plethora of immune functions depending on tissue distribution. Despite their known antitumor potential, they have been largely overlooked in the cancer field for their content paucity in cancer patients. I hypothesize that their scarce abundance and poor activation status is caused by cancer-induced immunosuppressive mechanisms. Indeed, I observed that circulating and metastasis-infiltrating iNKT cells are functionally impaired in the K14cre;Cdh1F/F;Trp53F/F(KEP)-based mouse model of de novo breast cancer metastases. With a translational approach, I will provide an unprecedented comprehensive dataset comparing iNKT cell immunophenotype in metastatic breast cancer patients and healthy controls. Next, I will generate human iNKT cell lines to perform in vitro mechanistic studies aimed at assessing how cancer-associated inflammation can modulate iNKT cell antitumor activity. Moreover, the innovative use of iNKT cell deficient Jα18-/- mice coupled to the KEP-based model of breast cancer metastases, will offer a clear picture of the role of iNKT cells and their cancer-associated cellular networks during the metastatic cascade. Finally, I will in vivo deplete immunosuppressive cells to unleash iNKT cell antitumor activity. My solid knowledge of iNKT cell biology combined with the expertise in breast cancer-associated inflammation of the hosting lab and the cutting-edge clinical research of the institute will uniquely generate fundamental knowledge with high applicative potential for the design of novel combinatorial immunotherapies for metastatic breast cancer.

Оригинален текст от CORDIS (на английски).

Участници

STICHTING HET NEDERLANDS KANKER INSTITUUT-ANTONI VAN LEEUWENHOEK ZIEKENHUIS · AmsterdamКоординаторНидерландия