Abstract
Immunotherapeutic approaches, including adoptive cell therapy, revolutionized treatment in multiple myeloma (MM). As dendritic cells (DCs) are professional antigen-presenting cells and key initiators of tumor-specific immune responses, DC-based immunotherapy represents an attractive therapeutic approach in cancer. The past years, various DC-based approaches, using particularly ex-vivo-generated monocyte-derived DCs, have been tested in preclinical and clinical MM studies. However, long-term and durable responses in MM patients were limited, potentially attributed to the source of monocyte-derived DCs and the immunosuppressive bone marrow microenvironment. In this review, we briefly summarize the DC development in the bone marrow niche and the phenotypical and functional characteristics of the major DC subsets. We address the known DC deficiencies in MM and give an overview of the DC-based vaccination protocols that were tested in MM patients. Lastly, we also provide strategies to improve the efficacy of DC vaccines using new, improved DC-based approaches and combination therapies for MM patients.
Highlights
Multiple myeloma (MM) is the second most common hematological malignancy
Upon deletion of either of these genes, the development of CD8α+ and CD103+ cDC1s was found to be defective, while CD11b+ cDC2 development remained unaffected. These findings suggest that the development of both the CD8α+ cDC1s in lymphoid tissue and the CD103+ cDC1s in non-lymphoid tissue depends on the same transcription factors [60]
MM patients, making MM-dendritic cells (DCs) not as potent in inducing an anti-MM response as HD-DC. Another explanation for defective DCs in MM patients could be the immunosuppressive activity of MM cells and the suppressive tumor microenvironment as cited earlier in this review. These findings suggest that ex-vivo-generated monocyte-derived DCs (moDCs) derived from MM patients are not the most convenient DC source for DC-based immunotherapy
Summary
Multiple myeloma (MM) is the second most common hematological malignancy. Due to the uncontrolled proliferation and subsequent accumulation of a single clone of terminally differentiated B cells in the bone marrow (BM) niche, advanced stages of MM are accompanied by clinical features, such as anemia, renal failure, and hypercalcemia in conjunction with osteolytic bone lesions [1]. Monoclonal antibodies, bispecific antibodies, immune checkpoint inhibitors, vaccines, and adoptive T cell therapies have been actively investigated, and some of them achieved remarkable clinical successes in MM patients [8]. Despite the advances in cancer immunotherapy, the majority of patients still relapse, and responses are hampered by immune escape mechanisms and the presence of an immunosuppressive. The use of dendritic cells (DCs) as a platform for cancer vaccine development is another safe and promising strategy to enhance tumor-specific host immune responses [25,26]. In the context of cancer, it is important to note that DCs can exert immunosuppressive and pro-tumoral effects either by an increased expression of immune checkpoints or by the elaboration of tolerogenic signals. Further details concerning the challenges, the opportunities, and the future directions of DC-based immunotherapy in MM are addressed focusing on the DC deficiencies in the BM niche, the currently used DC-based vaccination strategies in clinical trials, and the therapeutic potential of new, improved DC-based approaches, and combination therapies for MM patients
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