Assessment of the dynamics of immunological parameters at the beginning of therapy as prognostic and predictive factors in patients with melanoma


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Abstract

Background. The search for dynamic biomarkers of the effectiveness of immunotherapy is an important task in modern oncology. We analyzed the dynamics of individual immune cell subpopulations at the beginning of therapy as a predictor of the effectiveness of treatment. Objective. Assessment of the dynamics of the main subpopulations of lymphocytes and the possibility of its use as an early marker of response to therapy in patients with melanoma. Methods. The study included 182patients who received ipilimumab therapy and vaccine therapy (CaTeVac and Tag-7 genetically modified vaccines) for the treatment of locally advanced inoperable (10.4%) and metastatic (89.6%) melanoma. Evaluation of immunological parameters was carried out before treatment and after 2-6 weeks from its start. The indicators of increase and decrease in the studied immune cell populations were used as a predictor of the effectiveness of therapy. Factors that increase the likelihood of an objective response or reduce the risks of progression or death at P <0.05 were considered favorable. Results. The change in the lymphocyte and cytotoxic lymphocyte (CTL) count, decrease in the of NK cell, T-lymphocyte and CD25+ T-helper (Th) count, an increase in the number of neutrophils, neutrophil-lymphocyte ratio and immunoregulatory index, HLA DR+CTL, CD95+ lymphocytes were favorable prognostic factors. The unfavorable factors included an increase in the count of regulatory T-lymphocytes, Th and CD25+ Th (%), NKT cells and a decrease in the number of CD71+ lymphocytes. Changes in the count of memory cells, CD38+ Th, CD38+ CTL, CTLA4+ Th, CD1D+ lymphocytes, CD3-CD16+56+NKG2D+, CD3+CD4+ CD8+ and CD3+CD4-CD8- had no association with indicators of effectiveness at the study-specified level of significance. Conclusion. Monitoring of the state of the immune system during therapy can provide important information about the development of the treatment effect prior to the routine radiological assessment of the response according to the RECIST system.

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About the authors

A. V Novik

N.N. Petrov National Medical Research Center of Oncology; Saint Petersburg State Pediatric Medical University

Email: anovik@list.ru
Saint Petersburg, Russia

A. B Danilova

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

T. L Nekhaeva

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

N. V Emelyanova

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

A. I Semenova

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

D. Kh Latipova

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

G. M Teletaeva

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

S. A Protsenko

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

I. A Baldueva

N.N. Petrov National Medical Research Center of Oncology

Saint Petersburg, Russia

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