CLL crosstalk with naïve T cells enhances the differentiation of IL-22-producing T cells and CLL -cell survival

Abstract

Patients with chronic lymphocytic leukemia (CLL) exhibit clinical findings suggesting an altered immune system, with an increased risk of infection and the development of other cancers and various autoimmune phenomena. These associations are thought to be orchestrated in part by the interactions of leukemic cells with normal cells and elements in tissues, the latter referred to as the tumor microenvironment (TME). Notably, these interactions support the survival and expansion of CLL cells. Most well studied is the impact of the leukemic cells on T cells, leading to alterations in T-cell subset composition, surface membrane molecule expression, immune-synapse formation, and migration, along with functional changes such as exhaustion. Nevertheless, the molecular mechanisms by which differentiation of naive T (Tn) cells to various memory T-cell subsets occurs in CLL and the effects of imbalances of the process on leukemic B-cell survival and disease progression are not fully understood. Our results suggest a previously unrecognized positive loop involving IL-22-producing T cells, CLL B cells, and T cells in the TME that contributes to the maintenance of the leukemic clone and inuences patient outcomes. Deciphering this complex interplay within the CLL TME might provide insights that could inform future therapeutic strategies.