INFLUENCE OF REGULATORY T CELLS ON THE FUNCTIONING OF NATURAL KILLER CELLS DURING CANCER IMMUNOTHERAPY

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Abstract

One of the common arguments against cancer immunotherapy based on natural killer (NK) cells activated in the presence of interleukin-2 (IL-2) is the probability of the activation of regulatory T cells (Tregs) by IL-2 besides NK cells. Thus, we have monitored numbers of FoxP3+CD4+CD25+ T cells in the samples of healthy volunteers’ peripheral blood mononuclear cells (PBMCs) cultured with or without IL-2. We observed marked increase in the percentages of the CD4+CD25+ T cells in the presence of IL-2. Proportions of Foxp3+CD4+CD25+ T cells feebly increased, remained on the same level or even decreased compared to PBMCs cultured without exogenous IL-2. Based on the absence of FoxP3 expression, most of the CD4+CD25+ T cells purified from IL-2 activated PBMCs were not Tregs, but activated Th cells. Moreover, the addition of the purified supposed Tregs to samples of activated NK cells never inhibited their cytotoxic reactions.

 

About the authors

I. O. Chikileva

Establishment of the Russian Academy for Medical Sciences N.N. Blokhin Russian Cancer Research Center RAMS

Author for correspondence.
Email: irinatchikileva@mail.ru
кандидат биологических наук, младший научный сотрудник лаборатории клеточного иммунитета НИИ ЭДиТО ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН Адрес: 115478, Москва, Каширское ш., д. 2 Тел./факс: 8(495) 324-27-94 Россия

I. Zh. Shubina

Establishment of the Russian Academy for Medical Sciences N.N. Blokhin Russian Cancer Research Center RAMS

Email: irinashubina@mail.ru
кандидат биологических наук, старший научный сотрудник лаборатории клеточного иммунитета НИИ ЭДиТО ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН Адрес: 115478, Москва, Каширское ш., д. 24 Тел./факс: 8(495) 324-27-94 Россия

E. V. Kiselevskii

Establishment of the Russian Academy for Medical Sciences N.N. Blokhin Russian Cancer Research Center RAMS

Email: kisele@inbox.ru
доктор медицинских наук, профессор, заведующий лабораторией клеточного иммунитета НИИ ЭДиТО ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН Адрес: 115478, Москва, Каширское ш., д. 24 Тел./факс: 8(495)324-27-94 Россия

References

  1. Mule J.J., Shu S., Schwarz S.L., Rosenberg S.A. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science. 1984; 225: 1487–1489.
  2. Sallusto F., Lanzavecchia A. Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte-macrophage colony-stimulating factor plus interleukin-4 and down-regulated by tumor necrosis factor α. J. Exp. Med. 1994; 179: 1109–1118.
  3. Schadendorf D., Ugurel S., Schuler-Thurner B. et al. Dacarbazine (DTIC) versus vaccination with autologous peptide-pulsed dendritic cells (DC) in first-line treatment of patients with metastatic melanoma: a randomized phase III trial of the DC study group of the DeCOG. Ann. Oncol. 2006; 17: 563–570.
  4. Grabenbauer G.G., Lahmer G., Distel L., Niedobitek G. TumorInfiltrating Cytotoxic T Cells but not Regulatory T Cells Predict Outcome in Anal Squamous Cell Carcinoma. Clin. Cancer Res. 2006; 12 (11): 3355–3360.
  5. Shubina I.Zh., Demidov L.V., Chikileva I.O. et al. LAK immunotherapy in clinical studies. In: Kiselevsky M.V. (ed.). Atlas. Effectors of Antitumor Immunity. Springer. 2008. 101–111 p.
  6. Titov K.S., Demidov L.V., Kiselevskij M.V. i dr. Intraplevral’naya IL-2 immunoterapiya pacientov s metastatichiskimi plevritami. Ros. Onkol. Zh. 2010; 4: 20-24.
  7. Titov K.S., Shubina I.Zh., Volkov S.M. i dr. Immunoterapiya opuholevyh serozitov / Pod red. V.Yu. Sel’chuka, M.B. Bychkova, M.V. Kiselevskogo. Opuholevye serozity. Plevrity, ascity, perikardity. M.: Prakticheskaya medicina. 2011. 233-265 s.
  8. Kimura H., Iizasa T., Ishikawa A. et al. Prospective Phase II Study of Post-surgical Adjuvant Chemo-immunotherapy Using Autologous dendritic cells and activated killer cells from tissue culture of tumor-draining lymph nodes in primary lung cancer patients. Anticancer Research. 2008; 28: 1229–1238.
  9. Valteau-Couanet D., Leboulaire C., Maincent K. et al. Dendritic cells for NK/LAK activation: rationale for multicellular immunotherapy in neuroblastoma patients. Blood. 2002; 100: 2554–2561.
  10. Berdeja J.G., Hess A., Lucas D.M., O’Donnell P. et al. Systemic interleukin-2 and adoptive transfer of lymphokine-activated killer cells improves antibody-dependent cellular cytotoxicity in patients with relapsed B-Cell lymphoma treated with rituximab. Clin. Cancer Res. 2007; 13: 2392–2399.
  11. Ralainirina N., Poli. A, Michel. T. et al. Control of NK cell functions by CD4+CD25+ regulatory T cells. J. Leukoc. Biol. 2007; 81: 144–153.
  12. Fontenot J.D., Rasmussen J.P., Williams L.M. et al. Regulatory T cell lineage specification by the forkhead transcription factor foxp3. Immunity. 2005; 22: 329–341.
  13. Jiang S, editor. Regulatory T cells and clinical application. Springer. 2008. 586 p.
  14. Caligiuri M.A. Human natural killer cells. Blood. 2008; 112: 461–469.
  15. Allan S.E., Crome S.Q., Crellin N.K. et al. Activation-induced FOXP3 in human T effector cells does not suppress proliferation or cytokine production. International Immunol. 2007; 19: 345–354.

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