Mass cytometry dissects T cell heterogeneity in the immune tumor microenvironment of common dysproteinemias at diagnosis and after first line therapies

摘要: Dysproteinemias progress through a series of clonal evolution events in the tumor cell along with development progressively more “permissive” immune microenvironment (iTME). Novel multiparametric cytometry approaches, such as by time-of-flight (CyTOF) combined novel gating algorithms can rapidly characterize previously unknown phenotypes iTME tumors and better capture its heterogeneity. Here, we used 33-marker CyTOF panel to dysproteinemia patients (MGUS, multiple myeloma—MM, smoldering MM, AL amyloidosis) at diagnosis after standard care first line therapies (triplet induction chemotherapy autologous stem transplant—ASCT). We identify subsets, some which are unique absent from matched peripheral blood samples, potential roles immunosurveillance well escape. find that amyloidosis has distinct compared other dysproteinemias higher myeloid “innate-like” T subset infiltration. show senescence might be implicated disease pathogenesis trisomies. Finally, demonstrate early post-ASCT period is associated an increase senescent exhausted have implications for rational selection therapies.