B-cell specific expression of the murine Myd88L252P mutation correlates with the establishment of an immunosuppressive microenvironnement in Waldenstrom macroglobulinemia lymphoplasmacytic lymphoma

Abstract

Waldenstrom macroglobulinemia is a rare and indolent lymphoproliferative disorder genetically characterized by the presence of the L265P mutation in the MYD88 gene in nearly each case. Despite its slow progression, Waldenstrom macroglobulinemia remain incurable due to the lack of specific treatments. The importance of the tumour microenvironment was well documented since the last decade especially concerning the study of solid tumours, but the failures of the immune microenvironment are also experiencing growing interest for B cell lymphomas. In this study, we investigated the implication of some dysregulations of the immune microenvironment in Waldenstrom macroglobulinemia through our Myd88L252P mutated transgenic model, which may explain its progression. In essence, we highlighted the existence of multiple immune escape mechanisms that lead to T-cell exhaustion and participate to Waldenstrom disease progression. This work in animals opens up new prospects for the development of new therapeutic combinations in WM targeting reactivation of the immune system.