REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1613265
This article is part of the Research TopicMechanisms and Challenges in Cancer Immunotherapy Resistance: Bridging Extrinsic and Intrinsic FactorsView all 4 articles
Deciphering the Bone Marrow Microenvironment's Role in Multiple Myeloma Immunotherapy Resistance
Provisionally accepted
- 1University of Parma, Parma, Italy
- 2Department of Medicine and Surgery, Parma, Italy
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Multiple Myeloma (MM) is a malignant monoclonal gammopathy characterized by the proliferation of plasma cells (PC) in the bone marrow (BM). The tight cross-talk between the BM microenvironment and PC is the hallmark of MM. The BM microenvironment comprises a cellular compartment, consisting of hematopoietic and nonhematopoietic cells. The first includes myeloid cells, T-and Blymphocytes, natural killer (NK) cells, macrophages, and osteoclasts (OCs). In contrast, nonhematopoietic cell types include BM-derived mesenchymal stromal cells (MSCs), osteoblasts, adipocytes and endothelial cells. Besides the cellular compartment, there is a non-cellular compartment that includes extracellular matrix, growth factors, chemokines, and several cytokines. All these members play distinctive but interacting roles in the progression of MM and the drug response.MM remains an incurable disease, but in the last years immunotherapy has emerged as an important tool in the treatment of MM. The involvement of the BM microenvironment is a relevant barrier in the response to immunotherapy and in generating resistance. In this review, we provide an overview of the BM microenvironment perturbation in MM patients and how it can determine the possible resistance to immunotherapy, including monoclonal antibodies (mAbs), antibody-drug conjugates, chimeric antigen receptor T-cell (CAR-T), and bispecific T-cell engagers (BsAbs).
Keywords: Myeloma, Resistance, mesenchymal cells, car-t, bi-specific antibodies
Received: 16 Apr 2025; Accepted: 30 Jun 2025.
Copyright: © 2025 Iannozzi, Giuliani and Storti. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Nicola Giuliani, University of Parma, Parma, Italy
Paola Storti, University of Parma, Parma, Italy
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