Immunological impairment in multiple myeloma
Universita degli Studi di Catania
Division of Hematology, Az. Ospedaliero- Universitaria Policlinico, via Santa Sofia, 86, CAP 95123, University of Catania, Catania, Italy
Dott.ssa Cesarina Giallongo, dott. DanieleTibullo,
Dott.ssa Cesarina Giallongo, dott. DanieleTibullo,
English; Italian
4 weeks
Cities/Months Jan Feb Mar Apr May Jun Jul Augt Sep Oct Nov Dec
No No No No No No No Yes No No No No
Type of Research Project
- Clinical Project with Laboratory work
What is the background of the project?
Within the microenvironment, the host immune system has a pivotal role for the PC growth, proliferation, survival, migration and resistance to drugs and is responsible for some clinical manifestations of MM. In fact, dysfunction of immune system is an important feature of MM patients and leads to infections and increased 
tumor growth. Myeloid Derived Suppressor Cells (G-MDSC) in Multiple Myeloma has been shown. These cells are able to inhibit T-cell activation and function through different mechanisms that include release of arginase (Arg-1) and nitric oxide (NO) in the microenvironment. Due to a large overlapping between G-MDSC and mature granulocytes immunophenotype in humans, also mature neutrophils have suppressive function. ability to migrate, invade and secrete immune modulating factors is drastically affected by specific TLR-agonist engagement. MSC can polarize into two different types with distinct phenotypes defined MSC1 and MSC2. In particular, TLR4 stimulation polarizes MSC toward a pro-inflammatory MSC1 phenotype, while stimulation of TLR3 results in the polarization toward an immunosuppressive MSC2 phenotype. In acute myeloid leukemia and lung cancer TLR4+ MSC more powerfully inhibited NK cell function obstructing anti-tumor immunity functions.
What is the aim of the project?
The aim of the project is to investigate how neoplastic plasma cells and mature neutrophils of patients affected by Multiple Myeloma affect mitochondrial and metabolic fitness of T lymphocytes.
What techniques and methods are used?
- In the first step, cell culture techniques and analysis of transcriptome databases are used. - In the second step, to analyze metabolism of T-lympocytes and the neoplastic plasma activity, the serum samples of patients with multiple myeloma are collected and analyzed through ELISA (Enzyme-Linked Immuno Sorbent assay) technique. - In the third step, flow cytometry will be used to detect and measure physical and chemical characteristics of multiple myeloma cells. - In the fourth step, in order to analyze the systemic impact of neoplastic plasma cells on gene expression, in this project RT-PCR (Reverse transcriptase-polymerase chain reaction) is used: In RT-PCR, the RNA template is first converted into a complementary DNA (cDNA) using a reverse transcriptase. The cDNA is then used as a template for exponential amplification using PCR for gene expression.
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 is supposed to attend regularly the research internship, to be cooperative. It will be important to participate willingly to the activities, maybe giving new point of view to the tutor. Students will follow the entire process of the experiments and will be able with time to conduct experiment by him/herself. In addition students could follow the ward and outpatients activity and could be able to integrate information coming from the lab with clinical features of the patients.
Will there be any theoretical teaching provided (preliminary readings, lectures, courses, seminars etc)
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?
Are there any legal limitations in the student’s involvement
Type of students accepted
This project accepts:
- Medical students
- Graduated students (less than 6 months)
- Pre-Medical students from the American-British system
- Dasanu CA. Immune alterations in untreated and treated multiple myeloma. J Oncol Pharm Pract 2012; 18: 257-263.