The Tsoumakidou lab is committed to identify some of the mechanisms through which cancer cells suppress antigen presenting cells to evade adaptive immunity and to develop novel cancer immunotherapeutics. The laboratory has a strong clinical background and works simultaneously with the mouse and human system.

Maria Tsoumakidou, M.D., Ph.D. (Brief CV)

Subverting tolerance to cancer specific antigens.

All malignant tumors harbor nonsysnonymous mutations. If presented on MHC molecules, peptides containing these mutations could potentially be immunogenic (neoantigens). Lung cancers, the world’s leading cause of cancer death, have a particularly high number of somatic mutations. Clinical responses to immune checkpoint inhibitors are paralleled by an expansion of the pool of neoantigen-specific T cells, implying that tumor regression is achieved by activation of these rare cells. A novel and crucial need has arisen to effectively mobilize cancer-specific immunity. T cell priming is under the control of professional antigen presenting cells, the dendritic cells (DCs). Although DCs are considered promising immunotherapeutic targets, their expected potential has not been yet realized in the clinical setting, largely because tumors either exclude DCs or subvert them to tolerogenic states.

Our team studies mechanisms of tolerance to tumor antigens, focusing on the discovery of novel molecules that can be targeted to protect cancer antigen-presenting cells from diverging to tolerogenic states.


The specific aims of our lab are to
:

• characterize the heterogeneity of human intratumoral antigen-presenting cells on multiple integrated levels (transcriptomics, proteomics and function) to identify tumor-induced states

• induce in vivo perturbations to mouse systems to delineate mechanisms of tumor tolerance

• conduct pre-clinical studies to test the efficacy of novel immunotherapeutic modalities

To achieve our goals, we utilize in vivo mice models of onco-immunology, sophisticated functional immunological assays with patient-derived primary cells, including patient-derived tumor xenografts in humanized mice and high throughput profiling of primary intratumoral immune cells (next-generation sequencing technologies and CyTOF).

B.S.R.C. "Alexander Fleming"
34 Fleming Street, 16672 Vari, Greece
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