Changes in immune subsets during chemotherapy as prognosis biomarkers for multiple myeloma patients by longitudinal monitoring

Abstract

Multiple myeloma (MM) is a malignancy of plasma cells accompanied by immune dysfunction. This study aimed to provide a comprehensive and dynamic characterization of the peripheral immune environment in MM patients and find its diagnostic and prognostic values for therapy. The peripheral immune profiles of MM inpatients and healthy controls were assessed by flow cytometry. A longitudinal study of immune subsets was observed during cycles of chemotherapy. The diagnostic and prognostic models were established based on immune subsets by the absolute shrinkage and selection operator (LASSO) and multivariate regression. MM patients possessed an impeded immune landscape, including reduced activation of B cells, increased effective T cells and regulatory T cells (Tregs), augmented CD16 expression on monocytes and dendritic cell percentages, decreased CD56^dimCD16⁺ natural killer cells (NKs), and amplified CD56^bright and HLA-DR⁺ natural killer T cells (NKTs). Chemotherapy has different dynamic effects on specific cells, of which 2 cycles is the key turning point. NKT, dendritic cells, naïve Tc and Th cells, HLA-DR⁺ Tc cells, CD56^dim NKTs, CD16⁺⁺ monocytes, and CD25⁺ B cells could have the diagnostic value, and a prognostic model including neutrophils, naïve Tc cells, CD56^brightCD16^dim NKs, and CD16⁺ dendritic cells was established with acceptable accuracy. Our data showed dynamic and abnormal peripheral immune profiles in MM patients, which had prognostic values and could provide the basis for clinical therapy.

Keywords: Adaptive immunity; Immune subsets; Innate immunity; Multiple myeloma; Prognostic factors.