Mechanisms of Immunogenicity of ALK+ ALCL


Institute Gustave Roussy

Dr. Laurence Brugieres,
Dr. Veronique Minard

Supervisor

Publication Link (LB)

Immunology of ALCL

Research Interest

Laurence Brugieres, MD is a paediatric oncologist involved in ALCL trials since 1999. She is engaged in a research programme devoted to biological mechanisms involved in immunogenicity of ALCL in children and investigates immune responses against ALK according to the type of treatment given to the patients.

Adriana Petrazzuolo

Research student

ORCID Link

 

Research Interest

My name is Adriana and I come from Italy. I graduated with a master’s in “Biology for molecular, cellular and physiopathological research”, from the University of Roma Tre, motivated by the curiosity for the molecular mechanisms of diseases and my willingness to make a personal contribution to improve conditions of diseased patients. During my master’s I became particularly interested in Immunology. The fine equilibrium between the recognition and destruction of invaders and the protection of the organism’s own tissue is fascinating. Breakage of this equilibrium can cause infectious, autoimmune diseases or cancer, making me understand the importance of the mechanisms of immune protection to understand and act on the molecular mechanisms of diseases.  My master’s thesis at the Ludwig Institute for Cancer research allowed me to approach the field of cancer immunology studying the role of tumor immunosuppressive factors, such as galectins, within tumor microenvironment.  After a short experience in a biotech company, where I participated in developing novel cancer vaccines, I decided to pursue my career within the research field joining the ALKATRAS PhD program. I will work at the Gustave Roussy where I will study the immunogenicity of ALK positive lymphoma and possibly realize my dream to make a personal contribution to amerliorate treatment options of ALCL patients.

Research description

Recent data suggest a relationship between minimal residual disease and anti-ALK antibody response in ALK+ ALCL. Titre and kinetics of ALK antibodies represent prognostic markers in ALCL, with patients with a lower amount of antik-ALK positive ALCL and define the different anti-tumour immune response in individual patients.

Our specific aims include: Study of the polymorphism of the main genes of immunity including TLR4, P2X7, IFNy and perforin using qPCR; evaluate the impact of the immune system on the humoral response to ALK, circulating tumour cells at diagnosis, minimum residual disease and progrnosis of ALK+ ALCL; use a systematic approach to screen ALCL patients for 384 SNPs within immunity related genes to delineate additional candidates that could be involved in immunogenicity.

Expected Results:
Provide a rationale for combined chemo- and immunotherapy of ALK+ lymphoma; understand the differences in immune responses in ALCL patients; generation of novel prognostic markers and markers to stratify patients for different therapies.

Planned secondment(s):
Year 1: Sofigen (PO#10) – assessment of patient SNPs – 2 month;
Year 2: LBG (B#2) – access to TMA and other tissue samples for SNP array analysis – 1month

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