P4-20-03: T-Cell Cytokine Production Related to Progression of Breast Cancer Patients.

Abstract

Background: Impaired immunosurveillance and immune dysregulation contribute to the pathogenesis and progression of breast cancer (BC). Upon activation, T cells synthesize inflammatory cytokines such as TNF-α that can promote or inhibit tumor growth. We therefore investigated T-cell cytokine syntheses as a predictor of disease progression. Methods: We recruited 115 BC patients [25 with locally advanced breast cancer (LABC), 21 with metastatic breast cancer (MBC), 25 with non-metastatic inflammatory breast cancer (IBC), and 44 with metastatic IBC (mIBC)] and 31 healthy donors (HD) for this ongoing study. The tumor phenotype consisted of 69 hormone receptor (HR) positive (including 26 patients with HER2 positive disease), 16 HR negative but HER2+, 30 triple negative BC (TNBC). To evaluate T cell function, peripheral blood mononuclear cells from patients and HD were stimulated overnight with immobilized anti-CD3 and soluble anti-CD28 antibodies and assessed for the percentage of T cells that synthesized cytokines by multi-parameter flow cytometry. The associations of T cell cytokine production profile with patient progression free survival (PFS) were analyzed by Kaplan Meier Test. Results: The median follow-up (FU) of 113 evaluable patients was 14.1 months with a median time to relapse of 10.5 months; 54 patients had stable disease (SD) and 59 patients had progression of disease (PD). In the entire cohort, on univariate analysis, metastasis, IBC, stage, and previous treatment predicted for worse PFS (p< 0.05). In non-metastatic patients (LABC+IBC), absolute count of anti-CD3 activated CD8+ T cells producing IL-17 was significantly higher in the SD patients compared with patient with PD (p=0.038), but it did not predict PFS (p=0.073). Similarly in metastatic patients, anti-CD3 activated CD4+ T cells producing TNF-α were significantly higher in patients with SD (p=0.025) and was predictive of longer PFS (p=0.033). Considering all patients with IBC (IBC + mIBC), although patients with PD had significantly fewer (percent and absolute number) anti-CD3 activated T cells capable of producing cytokines, this immune impairment was mostly related to metastasis and previous treatment. However, the percentage of anti-CD3 activated CD8+ T cells producing TNF-α was an independent positive prognostic indicator of PFS (p=0.002). Conclusion: Higher than average cytokine syntheses by anti-CD3 activated T cells are significantly associated with longer PFS. These data are consistent with the hypothesis that an adaptive immune response can control disease progression. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-20-03.