Immunological consequences of immunization with tumor lysate vaccine and propranolol as an adjuvant: A study on cytokine profiles in breast tumor microenvironment

Immunol Lett. 2017 Jan;181:63-70. doi: 10.1016/j.imlet.2016.11.014. Epub 2016 Nov 27.

Abstract

In this study, we sought out to study the anti-cancer effects of propranolol (Pro) in combination with tumor lysate vaccine on lymphocyte proliferation activities as well as on IL-2, IL-4, IL-10, IL-12, IL-17 and IFN-γ cytokine concentration in the tumor microenvironment (TME). A tumor model was established in inbred Balb/C mice using transplantation of tumor to the flank of native mice. Tumor-bearing mice were immunized with lysate tumor cells (vaccine), a combination of Pro/Vaccine (Vac). Control groups consisted of tumor-bearing mice receiving only propranolol or PBS three times with one week interval via subcutaneous (s.c) injection. One week after the last immunization, tumor was removed, homogenate was prepared and the levels of IL-12, IL-17, 1L-2, IL-10, IL-4, IFN-γ cytokine concentrations were evaluated by commercial ELISA kits. In addition, spleen cell suspension was used for the lymphocyte proliferation assay using the BrdU method. Results from this study indicated that Pro/Vac had the ability to significantly increase lymphocyte proliferation, and to suppress tumor growth. Administration of breast tumor lysates with propranolol increased the concentration of IL-12, IL-17, 1L-2 and IFN-γ cytokines in tumor microenvironment. This study has proved the efficiency of propranolol as an adjuvant in combination with the tumor vaccine model on tumor suppression via cytokine pattern modulation in tumor microenvironment.

Keywords: Breast cancer; Cytokines; Propranolol; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic*
  • Animals
  • Breast Neoplasms / immunology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy
  • Cancer Vaccines / immunology*
  • Cell Line, Tumor
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Female
  • Immunization
  • Immunotherapy / methods
  • Lymphocyte Activation
  • Mice
  • Propranolol*
  • Tumor Burden
  • Tumor Microenvironment / immunology*

Substances

  • Adjuvants, Immunologic
  • Cancer Vaccines
  • Cytokines
  • Propranolol