Proliferative CD8 T-cells : A Novel Immune Microenvironmental Determinant of Outcomes in Multiple Myeloma
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Multiple myeloma (MM) remains incurable despite major therapeutic advances, and the tumor microenvironment (TME) plays an important role in disease progression. Since T-cell dysfunction is of particular importance in MM, we hypothesised that dysfunctional cytotoxic T cells may be associated with adverse outcomes. We conducted single-cell multi-omic sequencing of newly-diagnosed MM to identify TME determinants of progression free survival (PFS). In a discovery cohort, we identified a cluster of proliferative CD8+ cells whose proportion in the bone marrow was associated with inferior PFS, independent of clinical covariates. This association was validated in an independent validation cohort, as well as in a tissue microarray cohort using multiplexed immunofluorescence. These proliferative CD8+ cells showed inconsistent expression of T-cell exhaustion genes and had a gene expression profile overlapping with a similar population described in solid tumors. Our results show that proliferative CD8+ cells are an important mediator of adverse outcomes in MM, and motivate further investigation into the ontogeny and functional characteristics of this population.
