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Cited by 52Multiple Myeloma Research and TreatmentsImmunotherapy and Immune ResponsesProtein Degradation and Inhibitors

Understanding the Role of T-Cells in the Antimyeloma Effect of Immunomodulatory Drugs

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D'Souza, Criselle, Prince, H. Miles, Neeson, Paul J.·2021·Frontiers in Immunology
DOI 10.3389/fimmu.2021.632399PMC PMC7973099
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Abstract

Immunomodulatory drugs (IMiDs) are effective treatments for patients with multiple myeloma. IMiDs have pleotropic effects including targeting the myeloma cells directly, and improving the anti-myeloma immune response. In the absence of myeloma cells, lenalidomide and pomalidomide induce CD4+T cell secretion of IL-2 and indirect activation of Natural Killer (NK) cells. In the context of T cell receptor ligation, IMiDs enhance T cell proliferation, cytokine release and Th1 responses, both in vivo and in vitro. Furthermore, combination treatment of IMiDs and myeloma-targeting monoclonal antibodies eg. daratumumab (anti-CD38) and elotuzumab (anti-SLAMF7), checkpoint inhibitors, or bispecific T cell engagers showed synergistic effects, mainly via enhanced T and NK cell dependent cellular toxicity and T cell proliferation. Conversely, the corticosteroid dexamethasone can impair the immune modulatory effects of IMiDs, indicating that careful choice of myeloma drugs in combination with IMiDs is key for the best anti-myeloma therapeutic efficacy. This review presents an overview of the role for T cells in the overall anti-myeloma effects of immunomodulatory drugs.

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  • Following iMiD treatment and selective degradation of IKZF1, T cells increase production of IFN-γ, IL-21, and IL-2, enhancing the anti-tumor capability of the immune system.

    “Following iMiD treatment and the selective degradation of iKZF1, t cells increase their production of iFN-γ, il-21, and il-2 enhancing the anti-tumor capability of the immune system to target the cancerous plasma cells (gandhi et al. 2014;D'Souza et al. 2021;Bird and Pawlyn 2023) (Figure 5A, iii).”

    From From serendipity to strategy: molecular glue degraders in cancer therapeutics (2025) · cites this paper as D'Souza et al. 2021

    The Mechanism of Action section says IMiDs degrade IKZF1 and IKZF3, increasing T-cell IL-2 production. Immune Modulation by IMiDs also reports increased T-cell IFN-γ secretion and tumor-specific immunity. The passages do not report increased IL-21 production or link IKZF1 degradation specifically to the IFN-γ increase. (LLM, conf=0.88)

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Authors
D'Souza, C., Prince, H. M., & Neeson, P. J.
Affiliations
  • The Royal Melbourne Hospital (AU)
  • The University of Melbourne (AU)
Corresponding author
Neeson, Paul J.
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2021-03-05
Volume
12
Pages
632399-632399
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2021.632399
PMC
PMC7973099
OpenAlex
W3134577157
Cited by
52
References
5
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1.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Minerva Access (University of Melbourne) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Health and Medical Research Council
Topics
  • Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
Keywords
immunomodulators, multiple myeloma, T cells, lenalidomide, pomalidomide, CD4+ T cells, interleukin-2, natural killer cells, Th1 response, T cell receptor ligation, daratumumab, elotuzumab, bispecific T-cell engagers, immune checkpoint inhibitors, dexamethasone, combination therapy
MeSH terms
Drug Therapy, Combination, Humans, Immunologic Factors, Immunotherapy, Killer Cells, Natural, Multiple Myeloma, Plasma Cells, T-Lymphocytes, Drug Resistance, Neoplasm, Tumor Microenvironment

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

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