Maturation-Related and Functional-Associated Phenotypic Profile of Tumor T Cells in Mature/Peripheral T-Cell Neoplasms: Association With the Diagnostic Subtype of the Disease

Abstract

T-cell chronic lymphoproliferative disorders (T-CLPD) are a heterogeneous group of mature T-cell malignancies, the classification of which remains challenging. In this study, we classified tumor cells from 86 patients diagnosed with either T-CLPD (n = 81) or T-cell acute lymphoblastic leukemia (n = 5) into precise functional and maturation-associated compartments, based on their phenotypic similarities with their normal maturation-related and functional associated T-cell counterparts. A database was generated using blood samples from 6 sex- and age-matched healthy donors as a template for normal T-cell subset flow cytometric immunophenotypes, to which tumor cells of individual patients were compared. Except for nodal T follicular–helper cell lymphoma and adult T-cell leukemia/lymphoma, which showed phenotypes overlapping with that of T follicular–helper and T regulatory cells, respectively, all other T-CLPD displayed immunophenotypic profiles consistent with conventional T helper (Th) cells, with different maturation-associated profiles per diagnostic category. These included predominant naive/naive-central memory phenotypes in T-cell prolymphocytic leukemia to terminal effector cytotoxic cellular profiles in T-cell large granular lymphocytic leukemia; other T-CLPD diagnostic categories (mostly Sézary syndrome/mycosis fungoides) resembled the diverse memory T-cell subsets. Interestingly, immunophenotypically less-mature tumor cells (T-cell prolymphocytic leukemia) displayed more heterogeneous Th profiles, whereas those with memory T-cell profiles showed more consistent Th-associated patterns (eg, Th2 or Th17 in Sézary syndrome/mycosis fungoides), and the most mature neoplasms (eg, T-cell large granular lymphocytic leukemia) systematically displayed a Th1-like pattern, reflecting progressively lower plasticity for the more advanced tumor-associated maturation stages. These findings confirm the presence of distinct phenotypic patterns resembling specific maturation-associated and Th-related profiles of normal T cells among distinct diagnostic categories of T-CLPD, which might contribute to a more precise classification of T-CLPD.