Abstract 5589: T-cell cytokine production profile of breast cancer patients

Abstract

Abstract Background: Impaired immunosurveillance and immune dysregulation contribute to the pathogenesis and progression of breast cancer. We recently reported that breast cancer (BC) patients have compromised immunity with significantly fewer T cells, B cells, and dendritic cells compared to normal healthy donors. To further investigate immune function, T cells were assessed for their ability to synthesize cytokines prior to initiation of therapy and 3 months later. Methods: We recruited 46 BC patients [3 with locally advanced breast cancer (LABC), 13 with metastatic breast cancer (MBC), 15 have newly diagnosed inflammatory breast cancer (IBC), and 15 with metastatic IBC (MIBC)] and 13 healthy donors (HD) for this ongoing study. The tumor phenotype consisted of 28 hormone receptor (HR) positive (including 10 patients with HER2 positive disease), 7 HR negative but HER2+, 11 triple negative (TN). Thirty-nine patients are alive and have both baseline and follow up data at 3 months; 7 deceased patients had baseline data only. Peripheral blood mononuclear cells (PBMC) from patients and HD were stimulated overnight with immobilized anti-CD3 and soluble anti-CD28 antibodies and cytokine (IL-2, IL-4, IL-10, and IL-17, TNF-α, and IFN-γ) syntheses by activated (CD69+) CD4 and CD8 T cells were measured by multi-color flow cytometry. Statistical differences between the immunoresponses of patients and HD were analyzed by Mann-Whitney U test. Results: Compared with HD, IBC and MIBC patients had a statistically significantly lower percentage (%) of TNF-α+ CD8+ T cells (p=0.041 and p=0.037 respectively) at baseline. MIBC patients also had significantly lower % IFN-γ+ CD8+ T cells (p=0.046) than HD at baseline visit. But there were no significant differences among LABC, IBC, MBC, and MIBC patients. TN patients had statistically significantly lower % of IL-2+ CD4+ T cells (p=0.047) and TNF-α+ CD8+ T cells (p=0.041) at baseline than HD. The 7 deceased patients (3 IBC, 3 MIBC, and 1 MBC) had significantly lower %'s of CD4+ and CD8+ T cells that synthesized IL-2, TNF-α, IFN-γ, IL-4, and IL-10 than the 39 living patients (all p < 0.05) at baseline. At 3 months, all patient groups except IBC had T-cell responses that were similar to those of HD. Specifically, IBC patients had persistently significantly lower % of TNF-α+ CD8+ T cells than HD (p=0.048). Conclusion: In summary, T cell function is essential for maintaining immunosurveillance against tumor progression. Our data suggest that BC patient, especially IBC patients, have impaired T-cell responses and that therapeutic intervention may restore immune function only in a subset of those patients. Immunomodulatory therapy can play a role in IBC and contribute to improve patient outcome. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5589.