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

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.

• Authors: Denise L Cecil, Kyong Hwa Park, Ekram Gad, Jennifer S Childs, Doreen M Higgins, Stephen R Plymate, Mary L Disis
• Journal: Breast cancer research and treatment (Breast Cancer Res Treat) Vol. 139 Issue 3 Pg. 657-65 (Jun 2013) ISSN: 1573-7217 [Electronic] Netherlands
• PMID: 23749321 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antigens, Neoplasm
• Epitopes, T-Lymphocyte
• Immunoglobulin G
• Interferon-gamma
• Receptor, IGF Type 1

Topics

• Adult
• Aged
• Antigens, Neoplasm (immunology)
• Breast Neoplasms (immunology)
• Case-Control Studies
• Epitopes, T-Lymphocyte (immunology, pharmacology)
• Female
• Humans
• Immunoglobulin G (blood)
• Interferon-gamma (metabolism)
• Middle Aged
• Obesity (immunology)
• Overweight (immunology)
• Protein Structure, Tertiary
• Receptor, IGF Type 1 (chemistry, immunology)
• T-Lymphocytes, Helper-Inducer (immunology)
• Th1 Cells (drug effects, immunology)
• Th2 Cells (drug effects, immunology)