H2020Индивидуална стипендия2021–2023

CINPinCB · Deciphering tumor-promoting mechanisms mediated by neutrophils in vivo

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

Период: 2021-05-01 → 2023-04-30
Финансиране от ЕС: 203 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Неутрофилните клетки в туморната среда се изследват чрез генетични модификации при мишки, за да се разбере как определени гени стимулират растежа на рака. Това помага за разработването на нови стратегии за лечение на пациенти, които не реагират на сегашните терапии.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Deciphering tumor-promoting mechanisms mediated by neutrophils in vivo

Immunotherapies are revolutionizing cancer care but are only effective in a minority of patients. Because current treatments selectively target T lymphocytes, manipulating other cell types should create additional therapeutic opportunities. In this project, we focused on a myeloid cell population, the neutrophils, because they can be abundant in the tumor microenvironment, and their presence is often associated with a poor clinical prognosis. Consequently, patients who do not respond to current treatment options may benefit from novel therapeutic strategies targeting these cells. However, only some tumor-associated neutrophils promote tumor growth, and the complexity of these cells is not clearly understood, largely due to the experimental limitations inherent in studies of these cells. Therefore, novel approaches are needed to study tumor-associated neutrophils' mode of action. To address these knowledge gaps and experimental limitations, we began by studying human and murine tumors by single-cell RNA sequencing and histology to reveal the phenotypic complexity of tumor-associated neutrophils, and their conservation in both species. We then developed two experimental approaches to define the role of certain genes in the production of pro-tumor neutrophil responses: 1) we used CRISPR technology to genetically modify neutrophil progenitors that are then adoptively transferred into mice to study their functions in vivo; 2) we used genetic conditional mouse models to manipulate endogenous neutrophils in vivo. With these tools, we have identified several genes that appear to be required in the development of a pro-tumor neutrophil response. These results may have scientific and therapeutic significance, as they not only further our fundamental understanding of the mechanisms regulating neutrophil activities in cancer, but also point to new molecular targets for therapy.

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

Цел на проекта

Immunotherapies are revolutionizing cancer care, but are only effective in a minority of patients. Because current treatments typically target T lymphocytes, manipulating other cell types will create additional therapeutic opportunities. This research project aims to study neutrophils, because they can be abundant in the tumor environment, can modulate tumor outgrowth and response to treatments, and are candidate new therapeutic targets. However, tumor-associated neutrophils can be phenotypically and functionally heterogeneous, with only some of them promoting tumor growth. At present, we have a limited understanding of the complexity of neutrophils in tumors, and the mechanisms that control the functions of these cells. This is largely due to the inherent experimental limitations of neutrophil studies. Here, we will use a new approach to test the hypotheses that so-called Conditionally-Immortalized Neutrophil Progenitors (CINP) can be: 1) used to produce unrestricted numbers of tumor-associated neutrophils in vivo, and 2) gene-edited to study neutrophils mechanistically during cancer progression. Addressing these questions bears scientific and therapeutic importance, as it will not only deepen our fundamental understanding of the mechanisms regulating neutrophil activities in cancer, but also indicate new molecular targets for therapy. With this study, I will also create and share a publicly available database of all newly identified targets that will be investigated by us, other academic research groups, and industry. Besides, the project’s outputs will be communicated to the broader general public. Altogether, the training and input I will receive during the Marie Curie Individual Fellowship will prepare my transition from post-doc to independent researcher in an excellent scientific environment in Europe.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITE DE GENEVE · GeneveКоординаторШвейцария