Bystander Memory T Cells and IMiD/Checkpoint Therapy in Multiple Myeloma: A Dangerous Tango?

doi:10.3389/fimmu.2021.636375

Review

. 2021 Feb 15:12:636375.

doi: 10.3389/fimmu.2021.636375. eCollection 2021.

Bystander Memory T Cells and IMiD/Checkpoint Therapy in Multiple Myeloma: A Dangerous Tango?

Anne Marit Sponaas¹, Anders Waage^{1

2}, Esten N Vandsemb¹, Kristine Misund¹, Magne Børset^{1

3}, Anders Sundan¹, Tobias Schmidt Slørdahl^{1

2}, Therese Standal^{1

4}

Affiliations

¹ Department of Clinical and Molecular Medicine, Center for Myeloma Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
² Department of Hematology, St.Olavs Hospital, Trondheim, Norway.
³ Department of Immunology and Transfusion Medicine, St.Olavs Hospital, Trondheim, Norway.
⁴ Department of Clinical and Molecular Medicine, Center of Molecular Inflammation Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

PMID: 33679794
PMCID: PMC7928324
DOI: 10.3389/fimmu.2021.636375

Review

Bystander Memory T Cells and IMiD/Checkpoint Therapy in Multiple Myeloma: A Dangerous Tango?

Anne Marit Sponaas et al. Front Immunol. 2021.

. 2021 Feb 15:12:636375.

doi: 10.3389/fimmu.2021.636375. eCollection 2021.

Authors

Anne Marit Sponaas¹, Anders Waage^{1

2}, Esten N Vandsemb¹, Kristine Misund¹, Magne Børset^{1

3}, Anders Sundan¹, Tobias Schmidt Slørdahl^{1

2}, Therese Standal^{1

4}

Affiliations

¹ Department of Clinical and Molecular Medicine, Center for Myeloma Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.
² Department of Hematology, St.Olavs Hospital, Trondheim, Norway.
³ Department of Immunology and Transfusion Medicine, St.Olavs Hospital, Trondheim, Norway.
⁴ Department of Clinical and Molecular Medicine, Center of Molecular Inflammation Research, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.

PMID: 33679794
PMCID: PMC7928324
DOI: 10.3389/fimmu.2021.636375

Abstract

In this review article we discuss the role of the memory T cells in multiple myeloma (MM) and how they may influence immune responses in patients that received immunomodulating drugs and check point therapy.

Keywords: T cells; checkpoint therapy; immunomodulating drugs; multiple myeloma; virus.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

**Figure 1**
Illustrating re-activation of effector T-cells to viral antigens after combined IMiD and checkpoint therapy. (Created with BioRender.com).

See this image and copyright information in PMC

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References

1. Mateos MV, Orlowski RZ, Ocio EM, Rodriguez-Otero P, Reece D, Moreau P, et al. . Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study. Br J Haematol. (2019) 186:e117–21. 10.1111/bjh.15946 - DOI - PubMed
1. Mateos MV, Blacklock H, Schjesvold F, Oriol A, Simpson D, George A, et al. . Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. (2019) 6:e459–69. 10.1016/S2352-3026(19)30110-3 - DOI - PubMed
1. Usmani SZ, Schjesvold F, Oriol A, Karlin L, Cavo M, Rifkin RM, et al. . Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol. (2019) 6:e448–58. 10.1016/S2352-3026(19)30109-7 - DOI - PubMed
1. Guillerey C, Nakamura K, Vuckovic S, Hill GR, Smyth MJ. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies. Cell Mol Life Sci. (2016) 73:1569–89. 10.1007/s00018-016-2135-z - DOI - PMC - PubMed
1. Nakamura K, Kassem S, Cleynen A, Chretien ML, Guillerey C, Putz EM, et al. . Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment. Cancer Cell. (2018) 33:634–48.e635. 10.1016/j.ccell.2018.02.007 - DOI - PubMed

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[1] Mateos MV, Orlowski RZ, Ocio EM, Rodriguez-Otero P, Reece D, Moreau P, et al. . Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study. Br J Haematol. (2019) 186:e117–21. 10.1111/bjh.15946 - DOI - PubMed

[2] Mateos MV, Orlowski RZ, Ocio EM, Rodriguez-Otero P, Reece D, Moreau P, et al. . Pembrolizumab combined with lenalidomide and low-dose dexamethasone for relapsed or refractory multiple myeloma: phase I KEYNOTE-023 study. Br J Haematol. (2019) 186:e117–21. 10.1111/bjh.15946 - DOI - PubMed

[3] Mateos MV, Blacklock H, Schjesvold F, Oriol A, Simpson D, George A, et al. . Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. (2019) 6:e459–69. 10.1016/S2352-3026(19)30110-3 - DOI - PubMed

[4] Mateos MV, Blacklock H, Schjesvold F, Oriol A, Simpson D, George A, et al. . Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. (2019) 6:e459–69. 10.1016/S2352-3026(19)30110-3 - DOI - PubMed

[5] Usmani SZ, Schjesvold F, Oriol A, Karlin L, Cavo M, Rifkin RM, et al. . Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol. (2019) 6:e448–58. 10.1016/S2352-3026(19)30109-7 - DOI - PubMed

[6] Usmani SZ, Schjesvold F, Oriol A, Karlin L, Cavo M, Rifkin RM, et al. . Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol. (2019) 6:e448–58. 10.1016/S2352-3026(19)30109-7 - DOI - PubMed

[7] Guillerey C, Nakamura K, Vuckovic S, Hill GR, Smyth MJ. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies. Cell Mol Life Sci. (2016) 73:1569–89. 10.1007/s00018-016-2135-z - DOI - PMC - PubMed

[8] Guillerey C, Nakamura K, Vuckovic S, Hill GR, Smyth MJ. Immune responses in multiple myeloma: role of the natural immune surveillance and potential of immunotherapies. Cell Mol Life Sci. (2016) 73:1569–89. 10.1007/s00018-016-2135-z - DOI - PMC - PubMed

[9] Nakamura K, Kassem S, Cleynen A, Chretien ML, Guillerey C, Putz EM, et al. . Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment. Cancer Cell. (2018) 33:634–48.e635. 10.1016/j.ccell.2018.02.007 - DOI - PubMed

[10] Nakamura K, Kassem S, Cleynen A, Chretien ML, Guillerey C, Putz EM, et al. . Dysregulated IL-18 is a key driver of immunosuppression and a possible therapeutic target in the multiple myeloma microenvironment. Cancer Cell. (2018) 33:634–48.e635. 10.1016/j.ccell.2018.02.007 - DOI - PubMed

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Bystander Memory T Cells and IMiD/Checkpoint Therapy in Multiple Myeloma: A Dangerous Tango?

Affiliations

Bystander Memory T Cells and IMiD/Checkpoint Therapy in Multiple Myeloma: A Dangerous Tango?

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