Oncotarget

Research Papers:

Immunological monitoring for prediction of clinical response to antitumor vaccine therapy

Irina N. Mikhaylova, Irina Zh. Shubina _, George Z. Chkadua, Natalia N. Petenko, Lidia F. Morozova, Olga S. Burova, Robert Sh. Beabelashvili, Kermen A. Parsunkova, Natalia V. Balatskaya, Dmitrii K. Chebanov, Vadim I. Pospelov, Valeria V. Nazarova, Anastasia S. Vihrova, Evgeny A. Cheremushkin, Alvina A. Molodyk, Mikhail V. Kiselevsky and Lev V. Demidov

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Oncotarget. 2018; 9:24381-24390. https://doi.org/10.18632/oncotarget.25274

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Abstract

Irina N. Mikhaylova1, Irina Zh. Shubina1, George Z. Chkadua1, Natalia N. Petenko1, Lidia F. Morozova1, Olga S. Burova1, Robert Sh. Beabelashvili2, Kermen A. Parsunkova3, Natalia V. Balatskaya4, Dmitrii K. Chebanov5, Vadim I. Pospelov6, Valeria V. Nazarova1, Anastasia S. Vihrova1, Evgeny A. Cheremushkin1, Alvina A. Molodyk1, Mikhail V. Kiselevsky1 and Lev V. Demidov1

1N.N. Blokhin Russian Cancer Research Center, Moscow, Russia

2Laboratory of Genetic Engineering, Institute of Experimental Cardiology, Russian Cardiological Research and Production Complex, Moscow, Russia

3Diagnostic Laboratory Clinical Center “Optimum”, Sochi, Russia

4Department of Immunology and Virology, Moscow Helmholtz Research Institute of Eye Diseases, Moscow, Russia

5RUDN University, Moscow, Russia

6“Genetic Technologies and Analyses”, Moscow, Russia

Correspondence to:

Irina Zh. Shubina, email: irinashubina@mail.ru

Keywords: cancer vaccine therapy; melanoma; predictive markers; B2-microglobulin

Received: September 04, 2017    Accepted: March 22, 2018    Published: May 11, 2018

ABSTRACT

Immunotherapy has shown promising results in a variety of cancers, including melanoma. However, the responses to therapy are usually heterogeneous, and understanding the factors affecting clinical outcome is still not achieved. Here, we show that immunological monitoring of the vaccine therapy for melanoma patients may help to predict the clinical course of the disease.

We studied cytokine profile of cellular Th1 (IL-2, IL-12, IFN-γ) and humoral Th2 (IL-4, IL-10) immune response, vascular endothelial growth factor (VEGFA), transforming growth factor-β 2 (TGF-β 2), S100 protein (S100A1B and S100BB), adhesion molecule CD44 and serum cytokines β2-microglobulin to analyze different peripheral blood mononuclear cell subpopuations of patients treated with dendritic vaccines and/or cyclophosphamide in melanoma patients in the course of adjuvant treatment.

The obtained data indicate predominance of cellular immunity in the first adjuvant group of patients with durable time to progression and shift to humoral with low cellular immunity in patients with short-term period to progression (increased levels of IL-4 and IL- 10). Beta-2 microglobulin was differentially expressed in adjuvant subgroups: its higher levels correlated with shorter progression-free survival and the total follow-up time. Immunoregulatory index was overall higher in patients with disease progression compared to the group of patients with no signs of disease progression.


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