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Direct and indirect cross talk of mast cell with immunosuppressive tumor microenvironment
Universita degli Studi di Udine
Università di Udine - Dipartimento di Area Medica, Piazzale Massimiliano Kolbe, 4, Udine, 33100, Italia
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Although mast cells (MC)s are best known for their role in mediating allergic diseases, they play a role in many different processes, including clearance of enteric pathogens, food allergies, visceral hypersensitivity and intestinal cancer. Their involvement in tumor biology has been recognized and several recent studies have greatly contributed to clarify some important aspects of their function in the tumor microenvironment Studies in human patients have associated MCs function to either better or worst prognosis depending on tumor types and stages. Understanding inflammation to cancer transition is a long-cherished goal in the attempt to halt this deadly process. MCs, well-positioned to be one of the first immune cell to interact with environmental antigens, may play a role in gut carcinogenesis since they are typically located underneath the intestinal epithelium. MCs showing activated morphology exist in IBD specimens during the florid phase of inflammation and at this stage appear to contrast the microbiota-induced natural status of mild immunosuppression governing the gut homeostasis. This proposal stems from the idea that MCs play a role in the suppressive regulation of the inflammatory process influencing carcinogenesis through the recruitment and activation of immune regulatory cells.
What is the aim of the project?
1. Characterize the contribution of MCs in molding the microenvironment that promotes the tumor growth as well as the effects of tumor cells on immune system via MCs; 2. Study of the epigenetic and molecular differences in B cell populations with or without a suppressive phenotype; 3. Explore the effect of MC-exosomes on cancer cell behavior and immune immunosuppressive network.)
What techniques and methods are used?
The student will use cellular and molecular techniques direct to investigate the cellular events involved in the development of an immunosuppressive microenvironment. To achieve the stated goals, models of inflammatory and neoplastic diseases of the colon will be used. In vitro, 3D cultures of epithelial cells derived from the stem cells of intestinal crypts will be developed. The cultures will be disassembled and subsequently reconstituted together with cells of the immune system and the immunosuppressive role of regulatory cells will be studied and how to potentially modulate it. We will use cell cultures, flow cytometric analyzes, NGS gene expression and bioinformatics as well as electrophoretic gels and protein expression analysis in WB.
What is the role of the student?
- The student will mainly observe
- The student will observe the practical experiments but will be highly involved in the analysis of the results
- The tasks will be done under supervision
What are the tasks expected to be accomplished by the student?
The student will work in pair with the tutor if she/he is able, or he/she will follow the work of the tutor The student will perform basic lab research and it will be introduced to study of novel therapeutic approaches to chronic inflammation and cancer. disease. The student will achieve a methodological approach to the lab work including ethical issue as well as technical methods; this because an immunological laboratory uses techniques in relation to the objective that must be pursued and does not focus on the repetition of a single methodology for data collection.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
Scientific papers will be provided and the student will attend to lab meeting, in English.
What is expected from the student at the end of the research exchange? What will be the general outcome of the student?
- No specific outcome is expected
What skills are required of the student? Is there any special knowledge or a certain level of studies needed?
It will be appreciate if the student has basic knowledge of immunology, molecular biology and cellular biology and biochemistry at theoretical level at least.
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts: - Medical students
- - Frossi B; Rivera J; Hirsch E; Pucillo C. Selective activation of Fyn/PI3K and p38 MAPK regulates IL-4 production in BMMCunder nontoxic stress condition. J Immunol. 2007 Feb 15;178(4):2549-55.
- - Frossi B; De Carli M; Pucillo C. The cell: an antenna of the microenvironment that directs the immuneresponse.J Leukoc Biol. 2004 Apr;75(4):579-85.
- - Galli SJ; Nakae S; Tsai M. Mast cells in the development adaptive immune responses.Nat Immunol. 2005 Feb;6(2):135-42.
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