H2020Индивидуална стипендия2022–2025

MIRIC · Myeloid Cells: Investigating their Role for Immunotherapy in Cancer

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

Период: 2022-01-01 → 2025-03-01
Финансиране от ЕС: 203 149 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Молекулата Tim-3 и ролята на миелоидните клетки, като дендритните клетки и макрофагите, се анализират при борбата с рака. Това помага да се разбере как блокирането на Tim-3 влияе върху имунния отговор и ефективността на имунотерапията.

Този кратък обзор е генериран от изкуствен интелект

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

Резултати накратко

Myeloid Cells: Investigating their Role for Immunotherapy in Cancer

The checkpoint molecule Tim-3 is a co-inhibitory receptor that in recent years has been shown to mark the most severely “exhausted” or dysfunctional T cells. Largely stemming from work generated by my postdoctoral mentor, agents that interfere with Tim-3 signalling are now in development for clinical trials in cancer. However, Tim-3 is expressed on several different types of immune cells, and exactly how therapeutic blockade of Tim-3 might influence anti-tumour immunity was unknown. In conclusion, this work elucidated the cell autonomous and non-cell autonomous effects of Tim-3 deficiency in dendritic cells in anti-tumor immunity and dissected the relative contribution of DC versus monocytes & macrophages for effective ICT responses.

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

Цел на проекта

With more than 3.7 million new cases and 1.9 million deaths each year, cancer represents the second most important cause of death and morbidity in Europe with the estimated direct health cost increasing from €79 to €86 billion during 2005-2014. The emerging field of immune-checkpoint therapy (ICT) has demonstrated unprecedented responses in patients with several types of metastatic tumors that were previously resistant to available treatment options. However only ~13% of patients respond to the immunotherapy. I believe the primary reason for this is that most therapies are T cell directed and to achieve durable responses one must also engage the innate arm of the immune system. Myeloid cells constitute a major proportion of tumor infiltrating cells in human cancers and are essential for the induction of antigen specific T cell responses-cells which mediate anti-tumor immunity. Tim-3 is a check-point molecule that is not only expressed on T cells but also constitutively expressed on Dendritic cells, namely DC1, which are particularly adept at initiating protective anti-tumour immunity. A number of studies have highlighted the crucial role of DCs including analyses of The Cancer Genome Atlas showing that patient survival for many cancers correlates positively with the gene expression signature for DCs. Given the current activity in developing Tim-3 blocking agents for clinical translation, it is imperative that we have a full understanding of how modulation of Tim-3 affects the innate arm of the immune system. The aim of this proposal is to determine the cell-intrinsic and non cell-intrinsic effects of Tim-3 modulation in cancer. Furthermore we will analyze the cellular and transcriptional changes associated with tumour infiltrating DC after ICT with anti-Tim3. This proposal is highly interdisciplinary implementing single-cell 'omics' strategies and systems immunology approaches to further unravel the players and rules governing immune responses during malignancy.

Оригинален текст от CORDIS (на английски).

Участници

UNIVERSITAT BASEL · BaselКоординаторШвейцария