Immunomodulatory Drugs in the Context of Autologous Hematopoietic Stem Cell Transplantation Associate With Reduced Pro-tumor T Cell Subsets in Multiple Myeloma

Front Immunol. 2019 Jan 21:9:3171. doi: 10.3389/fimmu.2018.03171. eCollection 2018.

Abstract

Immunomodulatory drugs (IMiDs) are effective therapeutics for multiple myeloma (MM), where in different clinical settings they exert their function both directly on MM cells and indirectly by modulating immune cell subsets, although with not completely defined mechanisms. Here we studied the role of IMiDs in the context of autologous hematopoietic stem cell transplantation on the T cell subset distribution in the bone marrow of newly diagnosed MM patients. We found that after transplantation pro-tumor Th17-Th1 and Th22 cells and their related cytokines were lower in patients treated with IMiDs during induction chemotherapy compared to untreated patients. Of note, lower levels of IL-17, IL-22, and related IL-6, TNF-α, IL-1β, and IL-23 in the bone marrow sera correlated with treatment with IMiDs and favorable clinical outcome. Collectively, our results suggest a novel anti-inflammatory role for IMiDs in MM.

Keywords: anti-tumor and pro-tumor T cell subsets; autologous hematopoietic stem cell transplantation; bone marrow; immunomodulatory drugs; multiple myeloma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / pharmacology
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biomarkers
  • Combined Modality Therapy
  • Cytokines / metabolism
  • Female
  • Hematopoietic Stem Cell Transplantation* / methods
  • Humans
  • Immunomodulation / drug effects*
  • Immunophenotyping
  • Lymphocyte Count*
  • Male
  • Middle Aged
  • Multiple Myeloma / diagnosis
  • Multiple Myeloma / immunology*
  • Multiple Myeloma / therapy*
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology*
  • T-Lymphocyte Subsets / metabolism
  • Treatment Outcome

Substances

  • Antineoplastic Agents, Immunological
  • Biomarkers
  • Cytokines