Neuro-immune interactions in the oncogenesis of multiple myeloma and their therapeutical relevance

Česká verze

Authors: P.- Kotouček ^{1 3}; R. Enright ⁴; A. Orfao ⁵; J. Sedlák ^2,6
Authors place of work: Lekárska fakulta, Univerzita Komenského, Bratislava, Slovenská republika ¹; Biomedicínske centrum Slovenskej akadémie vied, Bratislava, Slovenská republika ²; Clinical Haematology, Broomfield Hospital, UK ³; Educational Psychology, University of Wisconsin and Madison, USA ⁴; Centro de Investigación del Cáncer, Salamanca, Španielsko ⁵; Nadácia Výskum Rakoviny, Bratislava, Slovenská republika ⁶
Published in the journal: Transfuze Hematol. dnes,27, 2021, No. 4, p. 306-315.
Category: Souhrnné/edukační práce
doi: https://doi.org/10.48095/cctahd2021306

Summary

Multiple myeloma is a malignancy originating from the immune system and the second most prevalent blood cancer. Myeloma cells derive from the process of somatic hypermutation in the post-germinal centre of lymph nodes. They migrate from the post-germinal centre to the bone marrow compartment where they completely suppress healthy hematopoietic stem cells. They settle in the haemopoietic stem cell niche by a specific process called “homing” taking control over all supportive stromal cells including the cells of the immune system, neurons and Schwann cells of the vegetative nervous system. Neurons of the sympathetic nervous systems end in the centre of each niche. Myeloma cells are fully supported by all these stromal cells in their proliferation and growth. We describe in this article the interactions between the neuro-immune system of the human body and the myeloma malignant plasma cells. Stromal neuro-immune cells stimulate the growth and proliferation of myeloma cells and new therapeutic interventions could reverse these interactions thus restoring the original immune surveillance in order to control myeloma. We describe the principles of immuno-chemotherapy in myeloma and its reinforcement using new interventions targeting these neuro-immune interactions.

Keywords:

Multiple myeloma – neuro-immune system – haemopoietic stem cell – myeloma stem cell – psychological distress of patients with myeloma

Zdroje

1. Adam Z, Klimeš J, Vorlíček J, et al. Maligní onemocnění, psychika a stres. Praha: Grada 2019.

2. Selye H. Stress and the General Adaptation Syndrome, British Med Journal. 1950; 1 (4667): 1383–1392.

3. Ader R, Cohen N. Behaviorally conditioned immunosuppression. Psychosom Med. 1975; 37 (4): 333–340.

4. Robert A, Cohen N. Psychoneuroimmunology: Conditioning and Stress. Annu Rev Psychol. 1993; 44: 53–55.

5. Pert CB, Ruff MR, Weber RJ, Herkenham M. Neuropeptides and their receptors: a psychosomatic network. J Immunol. 1985; 135 (2): 820s– –826s.

6. Russo AF. Overview of Neuropeptides: Awakening the Senses? Headache: J Head Face Pain. 2017; 57: 37–46.

7. Ruff M, Schiffmann E, Terranova V, Pert CB. Neuropeptides are chemoattractants for human tumor cells and monocytes: a possible mechanism for metastasis. Clin Immunol Immunopathol. 1985; 37 (3): 387–396.

8. Russignan A, Spina C, Tamassia N, et al. Endothelin-1 receptor blockade as new possible therapeutic approach in multiple myeloma. Br J Haematol. 2017; 78 (5): 781–793.

9. Hendricks L, Bore S, Aslina D, Morriss G. The effects of anger on the brain and body. Nat Forum J Counseling Addict. 2013; 2 (1)

10. Sakalová A, Štefániková Z, Kotouček P, et al. Súčasná liečba mnohopočetného myelómu a jej perspektívy. 1. vydanie, Bratislava, A-medi management 2016, 60 s.

11. Ondrušová M, Pšenková M, Suchanský, M. Vybrané epidemiologické aspekty mnohopočetného myelómu a zhubných nádorov plazmatických buniek. 2. aktualizované vydanie, Bratislava, Pharm-In 2018. 54 s.

12. McElwain TJ, Powles RL. High-dose intravenous melphalan for plasma-cell leukaemia and myeloma. Lancet. 1983; 2 (8354): 822–824.

13. Kotouček P. Slovenská myelómová spoločnosť. Available from: http: //myelom.sk/uploads/07_Pora%C4%8Fme%20sa/02_Komplement%C3%A1rna%20lie%C4%8Dba/Komplement%C3%A1rna%20lie%C4%8Dba%20pacientov%20s%20myel%C3%B3mom%20na%20Slovensku%202015.pdf. Accessed 22.5.2021

14. Krejcik J, Casneuf T, Nijhof IS, et al. Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma. Blood. 20161; 28 (3): 384–394.

15. Mateos MV, Cavo M, Blade J, Dimopoulos MA, et al. Overall survival with daratumumab, bortezomib, melphalan, and prednisone in newly diagnosed multiple myeloma (ALCYONE): a randomised, open-label, phase 3 trial. The Lancet. 2020; 395 (10218): 132–141.

16. Pessoa de Magalhães J, Vidriales MB, Paiva B, Orfao A, et al. Analysis of the immune system of multiple myeloma patients achieving long-term disease control by multidimensional flow cytometry. Haematologica. 2013; 98 (1): 79–86.

17. Barlogie B, Mitchell A, van Rhee F, Epstein J, Gareth JM, Crowley J. Curing myeloma at last: defining criteria and providing the evidence. Blood. 2014; 124 (20): 3043–3051.

18. Weisel K, Asemissen AM, Schieferdecker A, et al. Isatuximab, Carfilzomib, Lenalidomide and Dexamethasone (I-KRd) in front-line treatment of high-risk Multiple Myeloma: Results of the Safety Run-In cohort in the phase II, multicenter GMMG-CONCEPT trial RSS. Clinical lymphoma, myeloma & leukemia. 2019; 19 (10): e17.

19. Raje N, Berdeja J, Lin Y, Siegel S, et al. Anti-BCMA CAR T-Cell therapy bb2121 in relapsed or refractory multiple myeloma. N Engl J Med. 2019; 380: 1726–1737.

20. Hwa Y L, Shi Q, Dispenzieri A, et al. Beta-blockers improve survival outcomes in patients with multiple myeloma: a retrospective evaluation. Am J Hematol. 2017; 92 (1): 50–55.

21. Hwa YL, Lacy MQ, Gertz MA, Dispenzieri A, et al. Use of beta blockers is associated with survival outcome of multiple myeloma patients treated with pomalidomide. Eur J Haematol. 2021; 106 (3): 433–436.

22. Liu Y, Yu X, Zhuang J. Epinephrine Stimulates Cell Proliferation and Induces Chemoresistance in Myeloma Cells through the β-Adrenoreceptor in vitro. Acta Haematol. 2017; 138 (2): 103–110.

23. Knight JM, Rizzo JD, Hari P, et al. Propranolol inhibits molecular risk markers in HCT recipients: a phase 2 randomized controlled biomarker trial. Blood Adv. 2020; 4 (3): 467–476.

24. Cheng Y, Sun F, D‘Souza A, et al. Autonomic nervous system control of multiple myeloma. Blood Rev. 2021; 46: 100741.

25. Fielding C, Méndez-Ferrer S. Neuronal regulation of bone marrow stem cell niches. F1000Research. 2020; 9 (F1000 Faculty Rev): 614.

26. Calvo W. The Innervation of the bone marrow in laboratory animals. Am J Anatomy. 1968; 123 (2): 315–328.

27. Maryanovich M, Takeishi S, Frenette PS. Neural regulation of bone and bone marrow. Cold Spring Harb Perspect Med. 2018; 8 (9): a031 344.

28. Powell ND, Sloan EK, Bailey MT, et al. Social stress up-regulates inflammatory gene expression in the leukocyte transcriptome via β-adrenergic induction of myelopoiesis. Proc Natl Acad Sci U S A. 2013; 110 (41): 16574–16579.

29. Stakiw J, Bosch M, Goubran H. A closer look at the bone marrow microenvironment in multiple myeloma. Tumor Microenviron. 2018; 1: 1–8.

30. Lee SJ, Borrello I. Role of the immune response in disease progression and therapy in multiple myeloma. Cancer Treat Res. 2016; 169: 207–225.

31. Bruns I, Cadeddu RP, Brueckmann I, et al. Multiple myeloma-related deregulation of bone marrow-derived CD34 (+) hematopoietic stem and progenitor cells. Blood. 2012; 120 (13): 2620–2630.

32. Ghobrial I, Roccaro A, Azab AK, Runnels J, Leleu X. Trafficking of multiple myeloma cells: what regulates homing, adhesion, and mobilization of multiple myeloma to and from the bone marrow niches. Clin Lymphoma, Myeloma Leuk. 2009; 9 (2): 26–27.

33. Giannakoulas N, Ntanasis-Stathopoulos I, Terpos E. The role of marrow microenvironment in the growth and development of malignantp cells in multiple myeloma. Int J Mol Sci. 2021; 22 (9): 4462.

34. Jakubikova JD, Cholujova T, Hideshima P, et al. A novel 3D mesenchymal stem cell model of the multiple myeloma bone marrow niche: biologic and clinical applications. Oncotarget. 2016; 7 (47): 77326–77341.

35. Batty GD, Russ TC, Stamatakis E, Kivimäki M. Psychological distress in relation to site specific cancer mortality: pooling of unpublished data from 16 prospective cohort studies. BMJ. 2017; 356: 108.

36. Mols F, Husson O, Roukema JA, van de Poll-Franse LV. Depressive symptoms are a risk factor for all-cause mortality: results from a prospective population-based study among 3,080 cancer survivors from the PROFILES registry. J Cancer Surviv. 2013; 7 (3): 484–492.

37. Niazi S, Frank RD, Sharma M, et al. Impact of psychiatric comorbidities on health care utilization and cost of care in multiple myeloma. Blood Adv. 2018; 2 (10): 1120–1128.

38. Pyzer AR, Cole L, Rosenblatt J, Avigan DE. Myeloid-derived suppressor cells as effectors of immune suppression in cancer. Int J Cancer. 2016; 139: 1915–1926.

39. Leone P, Berardi S, Frassanito MA, et al. Dendritic cells accumulate in the bone marrow of myeloma patients where they protect tumor plasma cells from CD8+ T-cell killing. Blood. 2015; 126 (12): 1443–1451.

40. Rapoport A. Myeloma escape from immunity: an “inside” job. Blood. 2015; 126 (12): 1401–1403.

41. Kortüm M, Mai EK, Hanafiah NH, et al. Targeted sequencing of refractory myeloma reveals a high incidence of mutations in CRBN and Ras pathway genes. Blood. 2016; 128 (9): 1226–1233.

42. Keats J, Chesi M, Egan JB, et al. Clonal competition with alternating dominance in multiple myeloma. Blood. 2012; 120 (5): 1067–1076.

43. Rajkumar SV. Doublets, triplets, or quadruplets of novel agents in newly diagnosed myeloma? Hematology Am Soc Hematol Educ Program. 2012; 2012: 354–361.

44. Parrondo R, Sher T. 2019. Prevention of skeletal related events in multiple myeloma: focus on the RANK-L pathway in the treatment of multiple myeloma. Onco Targets Ther. 2019; 12: 8467–8478.

45. Morgan G, Davies FE, Gregory WM, et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet. 2010; 376: 1989–1999.

46. Anderson K, Ismaila K, Flynn PJ, et al. Role of bone-modifying agents in multiple myeloma: American Society of Clinical Oncology Clinical Practice Guideline Update.

J Clin Oncol. 2018; 36 (8): 812–818.

47. Ader R, Cohen N. Behaviorally conditioned immunosuppression. Psychosom Med. 1975; 37 (4): 333–340.

48. Scapagnini U. Psychoneuroendocrinoimmunology: The basis for a novel therapeutic approach in aging. Psychoneuroendocrino- logy.1992; 17 (4): 411–420.

49. Penedo FJ, Dahn JR, Kinsinger D, et al. Anger suppression mediates the relationship between optimism and natural killer cell cytotoxicity in men treated for localized prostate cancer. J Psychosom Res. 2006; 60 (4): 423–427.

50. Greer S, Morris T. Psychological attributes of women who develop breast cancer: A controlled study. J Psychosomatic Res. 1975; 19: 147–153.

51. Pettingale KW, Greer S, Tee DE. Serum IgA and emotional expression in breast cancer patients. J Psychosomatic Res. 1977; 21: 395–399.

52. Enright RD, Fitzgibbons R. Forgiveness therapy. Washington, 2015, DC, APA Books. 358 s.

53. Chapman B, Fiscella K, Kawachi I, Duberstein P, Muennig P. Emotion suppression and mortality risk over a 12-year follow-up. J Psychosom Res. 2013; 75 (4): 381–385.

54. Hansen MJ, Enright RD, Klatt J, et al. A palliative care intervention in forgiveness therapy for elderly terminally Ill cancer patients. J Palliat Care. 2009; 25 (1): 51–60.

55. Toussaint L, Barry M, Angus D, et al. Self-forgiveness is associated with reduced psychological distress in cancer patients and unmatched caregivers: Hope and self-blame as mediating mechanisms. J Psychosoc Oncol. 2017; 35 (5): 544–560.

56. Romero C, Friedman LC, Kalidas M, et al. Self-forgiveness, spirituality, and psychological adjustment in women with breast cancer. J Behav Med. 2006; 29 (1): 29–36.

57. Mickley JR, Cowles K. Ameliorating the tension: use of forgiveness for healing. Oncol Nurs Forum. 2001; 28 (1): 31–37.

58. Enright R. The Forgiving Life, APA Books 2012.

59. Kotouček P, Akobuk.sk. [online]. Available from: https: //akobuk.sk/terapia-odpustanim/.

60. Waltman MA, Russell DC, Coyle CT, et al. The effects of a forgiveness intervention on patients with coronary artery disease. Psychol Health. 2009; 24 (1): 11–27.

61. Joshy G, Thandrayen J, Koczwara B, et al. Disability, psychological distress and quality of life in relation to cancer diagnosis and cancer type: population-based Australian study of 22,505 cancer survivors and 244,000 people without cancer. BMC. 2020; 18: 372.

62. Islam S, Lee CD, Kim J, Enright R, Kotoucek, P. Marital status and survival in patients with multiple myeloma: The role of marriage in the management of multiple myeloma. Clin Oncol. 2019; 2 (3): 1–8.

63. Remembering Jimmie Holland, a Founder of Psycho-Oncology. [online]. Available from: https: //www.mskcc.org/news/remembering-jimmie-holland-founder-psycho-oncology.

64. IPOS 2021. [online]. Available from: https: //ipos2020.com/ipos2021/index.html.

65. Grassi L. Quam bene vivas referre: curing and caring in psycho- oncology. Psychooncology. 2013; 22 (8): 1679–1687.

66. Frankl VE. Napriek všetkému povedať životu áno. Eastone Books, 2021. 144 s.

67. Kotoucek P, Ezekwesili R, Hrianka M, Hriankova M, Nanistova E. Finding the meaning of life of patients with multiple myeloma correlates with better control of their disease by chemotherapy. Clin Lymphoma Myeloma Leuk. 2015; 15 (Suppl 3): e203–e204.

68. McLellan L, Pohlman B, Rybicki L, et al. Distress screening scores of malignant and benign hematology patients: results of a pilot project. Blood. 2012; 120 (21): 3173.

69. Fancourt D, Ockelford A, Belai A. The psychoneuroimmunological effects of music: a systematic review and a new model. Brain Behav Immunity. 2014; 36 (10): 15–26.

70. Bates D, Bolwell B, Majhail NS, et al. Music therapy for symptom management after autologous stem cell transplantation: results from a randomized study. Biol Blood Marrow Transplant. 2017; 23 (9): 1567–1572.

71. Schulman A. Waking the Spirit. New York: Pisador 2016.

72. Schmitz KH, Campbell AM, Stuiver MM, et al. Exercise is medicine in oncology: Engaging clinicians to help patients move through cancer.CA Cancer J Clin. 2019; 69 (6): 468–484.

73. Gristock J. The health benefits of three wheels. BMJ 2019; 364: k5192.

74. Fleischman SB, Homel P, Chen MR, et al. Beneficial effects of animal-assisted visits on quality of life during multimodal radiation-chemotherapy regimens. J Community Support Oncol. 2015; 13 (1): 22–26.

75. Keilani M, Kainberger F, Crevenna R et al. Typical aspects in the rehabilitation of cancer patients suffering from metastatic bone disease or multiple myeloma. Wien Klin Wochenschr. 2019; 131 (21–22): 567–575.

76. Pisu M, Demark-Wahnefried W, Kenzik KM, et al. A dance intervention for cancer survivors and their partners (RHYTHM). J Cancer Surviv. 2017; 11 (3): 350–359.