&amp;lt;i&amp;gt;In vitro&amp;lt;/i&amp;gt; analysis of T cell responses induced by breast tumor cell lysate pulsed with autologous dendritic cells

Nowruz Delirezh,Seyed Mohammad Moazzeni,Hamid Karbassian,Mohammad Ali Shokrgozar,Morteza Morteza Atri,Fazel Shokri

doi:10.4236/abb.2012.32019

Abstract

In this In vitro study, T cell responses induced by breast tumor cell lysate pulsed monocyte-derived DCs were analyzed in terms of proliferation, specific cytotoxicity and cytokine-release in order to use in immunotherapeutic settings. Nylon wool enriched T lymphocytes from 5 patients with breast cancer stimulated In vitro with tumor cell lysate pulsed monocyte-derived DCs and their proliferation response were analyzed by [3H] thymidine uptake test. Specific cytotoxic activity of tumor antigen primed T cells after three rounds weekly stimulation was evaluated by flow cytometry, and interferon-γ (IFN-γ) and interleukin-4 (IL-4) cytokines release assay was carried out 24 hours after last stimulation in the supernatant of primed T cells using commercially available ELI-SA kits. T cell proliferation assay revealed that tumor cell lysate pulsed DCs could stimulate autologous T cell proliferation response with stimulation indices 4.9 - 30. T cell mediated cytotoxicity assay demonstrated that tumor antigen primed T cells could significantly kill autologous tumor cells more than normal cells (P γ and IL-4 in response to restimulation by antigen pulsed DCs which were dominated by IFN-γ production in 2 and IL-4 production in 3 out of 5 patients. Our result suggested that breast tumor antigen pulsed DCs could elicit effective specific antitumor T cell responses In vitro, therefore, tumor antigen pulsed DC vaccination may be considered as a novel strategy for immunotherapy of patients with breast cancer refractory to standard modalities.

Highlights

Malignant breast cancer is the second leading cause of cancer death in women following lung cancer [1]
Our result suggested that breast tumor antigen pulsed Dendritic Cells (DCs) could elicit effective specific antitumor T cell responses in vitro, tumor antigen pulsed DC vaccination may be considered as a novel strategy for immunotherapy of patients with breast cancer refractory to standard mo
Human DC was generated from peripheral blood monocytes of 5 patients with stage III breast cancer (Table 1)

Summary

Introduction

Malignant breast cancer is the second leading cause of cancer death in women following lung cancer [1]. Immunotherapy is a therapeutic strategy that manipulates immune responses against tumor cells; this type of therapy is a new area of cancer therapies which directed at passively or actively against tumor cells [2]. The presence of DC at tumor site and regional lymph nodes pointed to a crucial role of these cells in antitumor immune responses [7,8]. Because of their unique capacity to stimulate resting T cells, DCs are the promising option for immunization protocols for the induction of antitumor immunity to patients with malignant disease [9,10,11]

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Results

Conclusion