Tumor-dependent Inflammation Modulation Increases Cancer Vaccine Efficacy

 

Trainee:

Rita-Marie T. Woodford

Woodford

Research Mentor:

Dr. Jenny Ting, PhD

Ting

Clinical Co-mentor:

Dr. Karen Mckinnon, PhD

Mckinnon

Clinical Co-mentor

Dr. Jon Serody, M.D.
Serody
Home Department Oral Biology
Project Description

Summary: Our lab examines inflammation in cancer and tumor-pulsed dendritic cell vaccine efficacy.  We find that tumor vaccines given to animals lacking a component of the caspase-1 activating inflammasome complex, ASC, resulted in complete reduction of tumor mass.  NLRP3, a binding partner to ASC in the caspase-1 activating inflammasome complex, induces an inflammatory response at the tumor site that nonetheless inhibits T lymphocytes from killing tumor cells.  This immune suppression is correlated with an increase of a population of cells called Myeloid-derived suppressor cells (MDSC).

Background: The NLRP3 protein expressed by antigen presenting cells normally forms a caspase-1 activating complex with an adaptor molecule, ASC, which activates pro-caspase-1.  Procaspase-1 undergoes self-cleavage to form the mature enzyme caspase-1, which cleaves the pro-inflammatory cytokines pro-IL-1b and pro-IL-18 into their mature forms.  My research will focus on this enzyme cascade in cancer.

Hypothesis: Components of the inflammasome reduce anti-tumor immunity.

Goal: This project is to improve cancer therapeutics by better understanding the mechanisms of inflammation and tumor immune evasion in the context of vaccination.

 

Click here for a copy of Rita-Marie's CV