Breast Cancer Research and Treatment

, Volume 139, Issue 3, pp 657–665

T-helper I immunity, specific for the breast cancer antigen insulin-like growth factor-I receptor (IGF-IR), is associated with increased adiposity

  • Denise L. Cecil
  • Kyong Hwa Park
  • Ekram Gad
  • Jennifer S. Childs
  • Doreen M. Higgins
  • Stephen R. Plymate
  • Mary L. Disis
Preclinical study

DOI: 10.1007/s10549-013-2577-z

Cite this article as:
Cecil, D.L., Park, K.H., Gad, E. et al. Breast Cancer Res Treat (2013) 139: 657. doi:10.1007/s10549-013-2577-z

Abstract

Numerous lines of evidence demonstrate that breast cancer is immunogenic; yet, there are few biologically relevant immune targets under investigation restricting the exploration of vaccines to limited breast cancer subtypes. Insulin-like growth factor-I receptor (IGF-IR) is a promising vaccine candidate since it is overexpressed in most breast cancer subtypes, is part of a dominant cancer growth pathway, and has been validated as a therapeutic target. We questioned whether IGF-IR was immunogenic in cancer patients. IGF-IR-specific IgG antibodies were significantly elevated in early-stage breast cancer patients at the time of diagnosis as compared to volunteer donors (p = 0.04). Predicted T-helper epitopes, derived from the IGF-IR extracellular and transmembrane domains, elicited a significantly higher incidence of Th2 immunity in breast cancer patients as compared to controls (p = 0.01). Moreover, the magnitude of Th2 immunity was greater in breast cancer patients compared to controls (p = 0.02). In contrast, both breast cancer patients and volunteer donors demonstrated a similar incidence of Th1 immunity to IGF-IR domains with the predominant response directed against epitopes in the intracellular domain of the protein. As the incidence of IGF-IR type I immunity was not associated with a breast cancer diagnosis, we questioned whether other factors were contributing to the presence of IGF-IR-specific T-cells in both populations. While age was not associated with Th1 immunity, we observed a significantly greater magnitude of IGF-IR IFN-γ-secreting T-cells in obese subjects as compared to overweight (p < 0.001) or healthy-weight (p = 0.006) subjects, regardless of breast cancer diagnosis. No significant difference was observed for Th2 incidence or magnitude when stratified by age (p = 0.174, p = 0.966, respectively) or body mass index (p = 0.137, p = 0.174, respectively). Our data demonstrate that IGF-IR is a tumor antigen and IGF-IR-specific Th1 immunity may be associated with obesity rather than malignancy.

Keywords

IGF-IRBreast cancer antigenTh1Th2Obesity

Supplementary material

10549_2013_2577_MOESM1_ESM.docx (100 kb)
Supplementary material 1 (DOCX 100 kb)

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Denise L. Cecil
    • 1
  • Kyong Hwa Park
    • 2
  • Ekram Gad
    • 1
  • Jennifer S. Childs
    • 1
  • Doreen M. Higgins
    • 1
  • Stephen R. Plymate
    • 3
    • 4
  • Mary L. Disis
    • 1
  1. 1.Tumor Vaccine GroupCenter for Translational Medicine in Women’s Health, University of WashingtonSeattleUSA
  2. 2.Division of Oncology/HematologyDepartment of Internal Medicine, Korea UniversitySeoulKorea
  3. 3.Department of MedicineUniversity of WashingtonSeattleUSA
  4. 4.GRECC and Research Service, Department of Veterans Affairs Medical CenterSeattleUSA