Novel immunophenotypic approaches to improve the diagnostic classification of mature T-cell neoplasms
Javier Morán Plata
Centro de Investigación del Cáncer. Universidad de Salamanca - CSIC
T-cell chronic lymphoproliferative disorders (T-CLPDs) comprise a highly heterogeneous group of neoplasms derived from mature or post-thymic T cells, accounting for 10–15% of non-Hodgkin lymphomas. The updated 2022 classifications (WHO and ICC) of lymphoid hematologic neoplasms include more than 25 diagnostic categories, many of which are characterized by aggressive clinical behavior and poor prognosis. The diagnostic classification of T-CLPDs remains challenging and poorly reproducible, due to significant overlap in the biological characteristics of clonal T cells across different categories, as well as to a high biological variability even within each category.
In this doctoral thesis, we aimed to identify novel phenotypic profiles to accurately distinguish and classify tumor cells by comparing them with the maturational and functional phenotypic patterns of normal T lymphocytes. This approach aimed to provide insights into the potential cellular origin of the tumor and, ultimately, to improve the current diagnostic classification. Additionally, we proposed investigating the tumor microenvironment of these neoplasms, through the analysis of the distribution of normal blood immune cells in three different subtypes of T-CLPD.
To achieve these objectives, we employed spectral flow cytometry to analyze 86 samples from patients diagnosed with different types of T-CLPDs; a total of 110 age- and sex-matched healthy donors were also included, as controls. In this seminar, the main findings of this research will be presented, which revealed different phenotypic patterns resembling specific maturation-associated and Th-related profiles of normal T-cells among the distinct diagnostic categories of T-CLPD; also, we observed differential profiles of immune impairment, which highly depended on the disease category.