Recruit · Origin and Function of Tumor-Associated Macrophages and Mesenchymal Stromal Cells in GBM Subtypes
„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“
- Период
- 2019-10-01 → 2022-11-30
- Финансиране от ЕС
- 261 192 €
- Участници
- 4
- Схема
- MSCA-IF
Линиите свързват координатора с партньорите.
Накратко на български
Глиобластомата и придружаващите я клетки, като макрофагите, се анализират, за да се разбере съставът на туморната среда. Това помага при избора на подходящи лекарства за различните видове пациенти чрез използването на животински модели.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Origin and Function of Tumor-Associated Macrophages and Mesenchymal Stromal Cells in GBM Subtypes
Glioblastoma (GBM) is the most common and aggressive primary tumor of the central nervous system. The median survival of patients with GBM remains less than 15 months. One of the key goals to understand GBM biology and find strategies to treat this deadly tumor is to define the different cell populations within the tumor. Our project aimed to characterize and understand more about tumor stroma in GBM. The identified new type of macrophages in ‘’Recruit’’ project has increased our understanding about brain tumor biology and push us to continue further investigating its origin and think about combining other type of drugs (have been previously used to inhibit bone resorption) to change the microenvironment! The acquired experience in molecular field and preliminary data obtained in ‘’Recruit’’ project beside my deep knowledge in tumor stroma and immunotherapy field will be the corner stone to start my own research and establish unique preclinical settings for therapeutic testing. Also, I have the skills that cover most of the stages from receiving tissue from patients, processing it, cultivating cells, making vaccine, immune monitoring and preparing protocols and final report for preclinical trials. This will help me to establish translational therapeutic projects in the future. Furthermore, the currently acquired knowledge will help me to establish these glioma models in any lab in Sweden and open possibilities of new projects. As these animal models represent the three patient subtypes, we hope to use these models in testing the efficacy of certain drugs, and predict which patient subtypes might benefit from this treatment more precisely. We and others believe that the genetic profiling of tumors will have great application in future therapy. These models hold great hope for preclinical trials for immunotherapy that is effective only in a subset of patients which could be attributed to the response rate that correlates with patient’s subtype. Furthermore, the short mentoring task and teaching medical students has added to my mentoring/teaching skills. Also, literature screening and writing a review about immunotherapy during lockdown time has increased my knowledge about most promising immunotherapy strategies.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
One of the key goals to understand GBM biology and find strategies to treat this deadly tumor is to define the different cell populations within the tumor. The inter-tumor heterogeneity among GBM patients, investigated on a molecular level, has led to the identification of three main subtypes; the proneural (PN), mesenchymal (MES), and classical (CL), which are associated with specific mutations. The different properties of the three subgroups play an important role in the clinical response and the pathology of the tumor. The tumor microenvironment, that play an important role in tumor heterogeneity, is built up by multiple factors including recruited cells, blood vessels, secreted cytokines, and extracellular matrix. However, the constitution of these factors in each subtype is not known. In this work, we will characterize the cells that are recruited to the different GBM subtypes focusing on tumor-associated macrophages (TAMs) and mesenchymal stromal cells (MSCs). For this purpose, transgenic mice representing the three glioma subtypes will be used. Chimeric mice will be utilized to investigate the origin of the recruited cells. Flow cytometry, confocal analysis, multiplex assays and single-cell gene expression analysis will be used to characterize the tumor cells and the recruited cells to find master regulatory elements of recruitment. Therapeutic targeting will follow identification of master regulatory factors that recruit TAMs and MSCs to the tumor.
Оригинален текст от CORDIS (на английски).
Участници
- KAROLINSKA INSTITUTET · STOCKHOLMКоординаторШвеция
- EMORY UNIVERSITY NON PROFIT CORP · AtlantaСъединени щати
- GOETEBORGS UNIVERSITET · GoeteborgШвеция
- ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · NEW YORKСъединени щати
Връзки
Данни: CORDIS, © Европейски съюз
