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Origin and Function of Tumor-Associated Macrophages and Mesenchymal Stromal Cells in GBM Subtypes

Periodic Reporting for period 1 - Recruit (Origin and Function of Tumor-Associated Macrophages and Mesenchymal Stromal Cells in GBM Subtypes)

Reporting period: 2019-10-01 to 2021-09-30

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.
I got training and experience in establishing transgenic glioma mouse models and several molecular techniques including growing plasmids, injecting virus, breeding transgenic mice, genotyping, large scale qPCR, and processing brain samples for proteomics. Preliminary obtained data will be the corner stone to start ''Tumor Stroma'' lab in US and collaboration were established to continue what we started in our ''Recruit'' project
The experience in molecular field and preliminary data I got bedside my deep knowledge in tumor stroma field and immunology will be the corner stone to start my own research. The novel unexpected origin of recruited cells will increase our understanding about brain tumor biology and push us to think about combining other type of drugs (have been previously used to inhibit bone resorption) to treat glioblastoma which is my ultimate goal!
Figure 1. Tartrate-resistant acid phosphatase (TRAP) staining showing skull marrow with quite high T