Regression of Triple-Negative Breast Cancer in a Patient-Derived Xenograft Mouse Model by Monoclonal Antibodies against IL-12 p40 Monomer

Cells. 2022 Jan 13;11(2):259. doi: 10.3390/cells11020259.


Although some therapies are available for regular breast cancers, there are very few options for triple-negative breast cancer (TNBC). Here, we demonstrated that serum level of IL-12p40 monomer (p40) was much higher in breast cancer patients than healthy controls. On the other hand, levels of IL-12, IL-23 and p40 homodimer (p402) were lower in serum of breast cancer patients as compared to healthy controls. Similarly, human TNBC cells produced greater level of p40 than p402. The level of p40 was also larger than p402 in serum of a patient-derived xenograft (PDX) mouse model. Accordingly, neutralization of p40 by p40 mAb induced death of human TNBC cells and tumor shrinkage in PDX mice. While investigating the mechanism, we found that neutralization of p40 led to upregulation of human CD4+IFNγ+ and CD8+IFNγ+ T cell populations, thereby increasing the level of human IFNγ and decreasing the level of human IL-10 in PDX mice. Finally, we demonstrated the infiltration of human cytotoxic T cells, switching of tumor-associated macrophage M2 (TAM2) to TAM1 and suppression of transforming growth factor β (TGFβ) in tumor tissues of p40 mAb-treated PDX mice. Our studies identify a possible new immunotherapy for TNBC in which p40 mAb inhibits tumor growth in PDX mice.

Keywords: IL-12p40 monomer; immunotherapy; patient-derived xenograft mouse model; triple-negative breast cancer; tumor-associated macrophage.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / drug effects
  • CD8-Positive T-Lymphocytes / immunology
  • Female
  • Humans
  • Immunotherapy
  • Interferon-gamma / metabolism
  • Interleukin-12 / blood
  • Interleukin-12 / metabolism
  • Interleukin-12 Subunit p40 / blood
  • Interleukin-12 Subunit p40 / immunology*
  • Interleukin-23 / blood
  • Interleukin-23 / metabolism
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Mice
  • Mice, Inbred NOD
  • Mice, SCID
  • Neutralization Tests
  • Spleen / metabolism
  • Triple Negative Breast Neoplasms / blood
  • Triple Negative Breast Neoplasms / drug therapy*
  • Up-Regulation
  • Xenograft Model Antitumor Assays*


  • Antibodies, Monoclonal
  • Interleukin-12 Subunit p40
  • Interleukin-23
  • Interleukin-12
  • Interferon-gamma