Kimon Argyropoulos, MD

Mature T-cell lymphomas (TCL) comprise a rare and heterogenous group of hematological neoplasms, characterized by clonal proliferation of malignant post-thymic T-cells. Compared to the well studied B-cell lymphomas, the pathobiology of TCL is to date poorly understood. As a result, a lack of distinct morphological, immunophenotypic and genetic features impedes pathologic and clinical diagnosis, while prognosis remains poor in the majority of cases.

Until now, no extensive studies have been made to approach TCL at the level of signaling networks. In a group of diseases lacking specific markers, the identification of dysregulated pathways could be applied for disease prognostication or even in developing novel therapeutic agents. Based on an ongoing collaborative study of M. Lia Palomba and Grégoire Altan-Bonnet on the signalosome of chronic lymphocytic leukemia, we hypothesize that specific phosphoprofiles elicited by various stimuli could have a significant discriminative capacity between TCL subtypes, cell subpopulations within the same neoplasm and malignant from normal T-cells. For this purpose, all phosphoresponses are assessed at a single-cell level through complex immunophenotyping and multiplexed phosphoflow cytometry. A second goal of this study is to perform extensive immunological profiling of TCL subtypes. Most data in this field are based on histopathological studies or in-vitro studies with cell lines, which both have translational limitations. By taking advantage of the single-cell level approach that flow cytometry offers, we are interested in assessing TCR repertoires of the malignant clones, the cellular origin and phenotypic plasticity of TCL subtypes and finally the role of the tumor microenvironment in disease progression and prognosis.