Abstract 3835: Impaired pSTAT3 and pSTAT5 induction by IL-2 does not affect IFNγ production in NK cells of breast cancer patients

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Abstract Although pSTAT3 and pSTAT5 in tumors have oncogenic potential, STAT dysregulation has not been extensively investigated in peripheral blood lymphocytes (PBL) of breast cancer patients. Alterations in JAK-STAT pathway in cancer patients contribute to immunosuppression and inadequate antitumor immune response. In this study baseline level and cytokine-mediated activation of pSTAT3 and pSTAT5 were investigated in PBL of breast cancer patients and healthy controls after in vitro treatment with IL-2 for 24h at 37C. Induction of pSTATs was assessed in cellular lysates by Western blotting using anti-pSTAT antibodies. PBL of breast cancer patients and controls were analyzed for intracellular IFNγ, CD3 and CD16 receptor expression and NK cell activity using Flow cytometry and 51Cr-release assay, respectively. The induction of pSTAT3 and pSTAT5 in PBL by IL-2 is significant for controls and patients, although the effect in patients is lower. Moreover, PBL and CD3-CD16+ NK cells of breast cancer patients compared to controls have significantly lower baseline level of IFNγ. IL-2 significantly increases the production of IFNγ in PBL inspite of impaired induction of pSTAT3 and pSTAT5 in breast cancer patients. Evaluation of NK cell subset shows highly significant induction of IFNγ by IL-2 in breast cancer patients and in healthy controls. Inspite of this, we found that NK cell activity of breast cancer patients is significantly lower compared to healthy controls suggesting that NK cell activity is more dependent on STATs inducibility than IFNγ production in these patients. These results provide evidence that evaluation of STAT expression and cytokine induction in PBL of breast cancer patients could be of diagnostic and therapeutic significance during non-specific active immunotherapy. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. 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 3835.