Research group - Dhifaf Sarhan

Immunotherapy for cancer has revolutionized the clinical practice, however, it is inefficient in more than 60% of all cancers due to highly immune-suppressive tumor microenvironment (TME) orchestrated by immune suppressor cells, which limit the infiltration of tumor-targeting immune cells, alternatively inhibit antigen-presentation and cytotoxic cell anti-tumor activity in situ resulting in ineffective immunotherapies. Here is a brief introduction to main projects of our group:

Project I: Adaptive NK cell immunological memory in solid tumors

For decades NK cells were believed to lack the immunological memory, however recent groundbreaking research by us and others revealed the opposite. We discovered novel mechanisms used by a subset of NK cells with immunological memory, called adaptive NK cells, to resist the suppressive tumor environment. In this project we focus on investigating the molecular mechanisms behind NK cell memory to tumors and the crosstalk with antigen presenting cells like dendritic cells and B cells in cancer. 

Project II: Antibody targeting of suppressive myeloid cells for cancer immunotherapy

The goal for this project is to identify specific targets for tumor-associated macrophages and myeloid-derived suppressor cells to reprogram their suppressive nature and later develop target antibodies to relieve the anti-tumor activity of NK cells and T cells. Currently we are studying G-coupled protein receptors as therapeutic targets in GI-tract cancers. 

Project III: Study the mechanisms of immune exclusion in advanced tumors highly infiltrated by myeloid cells

In this project, we study the myeloid cell-dependent inhibitory mechanisms of NK and T cell infiltration into cold and immune excluded pancreas tumors. Patient tumor and blood specimens are provided by national and international collaborators. Further, we are extensively examining the receptor signal integration in suppressive myeloid cells.

Project IV: Studies of sexual immune dimorphism in the TME

We found that a g-coupled protein receptor has predictive value for female cancer patients. Hormone regulation of this receptor function has been shown to induce anti-inflammatory properties in macrophages. This receptor impacts the immune landscape in TME biased by gender dimorphism. Extensive examination of the signal integration is needed to further elucidate its mechanism of action and clinical impact.

Research Group Leader Dhifaf Sarhan