Autologous dendritic cells and activated cytotoxic T‑cells as combination therapy for breast cancer

Oncol Rep. 2020 Feb;43(2):671-680. doi: 10.3892/or.2019.7435. Epub 2019 Dec 16.

Abstract

Breast cancer is the most common oncological pathology in women worldwide. Techniques for improving the clinical parameters of patients undergoing combination therapy for breast cancer are currently under development. A type of treatment employing dendritic cells (DCs) and cytotoxic DC‑induced antigen‑specific T lymphocytes efficiently eliminates residual cancer cells that are the key cause of tumor recurrence and metastasis. In the present study, DCs and activated lymphocytes (treated with IL‑12 and IL‑18) were isolated from the peripheral blood of patients with breast cancer, using a lysate of tumor tissue as antigen. The patients received the cells as part of adjuvant or neoadjuvant regimens (stage IV disease or progression). Evaluation of immunity was performed at 3 and 6 months after terminating immunotherapy. Evaluation of the disease‑free period was performed for 3 years after surgery. The use of antigen‑loaded autologous DCs combined with mononuclear cells with increased cytotoxic activity following Th1 polarization reduced the populations of immunosuppressive cells. The results of the present study demonstrated that the investigated cellular immunotherapy for breast cancer is safe, reduces the risk of relapse and metastasis, and improves immunity by reducing the number of regulatory T cells. Therefore, this therapeutic strategy may represent a novel approach to combating distant metastases of breast cancer.

Keywords: breast cancer; dendritic cells; cytotoxicity; cytotoxic T lymphocytes; T-helper cell polarization; cancer immunotherapy.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Aged
  • Breast Neoplasms / immunology
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Combined Modality Therapy
  • Dendritic Cells / immunology
  • Dendritic Cells / transplantation*
  • Female
  • Humans
  • Interleukin-12 / immunology*
  • Interleukin-18 / immunology*
  • Lymphocyte Activation
  • Middle Aged
  • Neoplasm Staging
  • Prospective Studies
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / pathology
  • T-Lymphocytes, Cytotoxic / transplantation*
  • Transplantation, Autologous
  • Treatment Outcome

Substances

  • Interleukin-18
  • Interleukin-12