IMS 2025 | Longitudinal multi-omic profiling uncovers immune escape and predictors of response in myeloma

So we utilize single-cell RNA sequencing of the immune system as well as RNA and whole-genome sequencing of the plasma cells from diagnosis to response to therapy and then disease progression to get a sense of what changes are associated with good outcomes and then what changes occurred at relapse in order to allow the myeloma to interrupt the way that the immune system is trying to work. The big things that we found were that naive B-cells seem to be a really important population at the post-stem cell transplant time point, where their expression and their abundance of genes that allow them to both proliferate and then migrate throughout the body could be a really valuable prognostic indicator of sustained response. And then looking ahead of that to when patients eventually progressed and relapsed, we saw that there was enrichment of cancer-testis antigen genes among a couple of other molecular hallmarks like expression of aberrant cytokines and chemokines and proliferative markers that seemed to associate with the positive change before of having more naive B-cells was then undone by this cancer-testis antigen-enriched myeloma, potentially through some of these mechanisms like cytokine and chemokine expression. The most important finding out of this that could be used in that way is the highly enriched cancer-testis antigen-expressing myeloma. The big thing in what future work needs to be done is to just really parse out how each of the different families of cancer-testis antigens influences the malignant features we observed in myeloma. For example, the aberrant expression of cytokine and chemokine genes and their proliferative markers. Cancer-testis antigens are such broad genes and there’s so many of them that our findings don’t necessarily connect an individual family to a biological function. So I think starting there to determine which cancer-testis antigens influence which problematic phenotypes in the myeloma cells would be a great further research to start and then once that’s completed, that will open up the door to so many different targets that could be used to directly get after this more problematic myeloma that’s observed preferentially at the progression time point.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.