Decreased Functions Of Natural Killer Cells In Peripheral Blood Of Advanced Triple Negative Breast Cancer Patients

Background : Natural killer (NK) cells are a major player in innate immune response. Two distinct NK cell subsets with different functions as the strongest cytotoxic activity (CD56dimCD16+) or cytokine production (CD56brightCD16+/-) have been known. In this study, we evaluated the phenotypic and functional difference of NK cells in peripheral blood (pB) from the patients who had advanced triple negative (TN) breast cancer compared to healthy controls. Methods : We enrolled advanced triple negative (TN) breast cancer patients treated at the National Cancer Center, Korea between March 2012 and March 2014. Healthy controls who visited for health screening were recruited at the same time period and peripheral blood (pB) samples were collected. In patient groups, pB was sampled either prior to the initiation or during the courses of chemotherapy. Then, patients were retrospectively classified into two groups as follows; non-responders (the group A) and responders (the group B) to the treatment. NK cells were isolated from peripheral blood mononuclear cells (PBMC) and analyzed based on their expression of CD56 and CD16. We looked at cytotoxic activity of pB NK cells against K562 cell line and measured CD107a expression as a parameter of NK cell activation. Results : The absolute numbers of lymphocytes and NK cells per cubic millimeter of pB were similar among healthy controls (N=24), the group A (N=16), and the group B (N=21). There was no significant difference in the proportion of pB NK cell subsets among three groups except CD56brightCD16+/- subset which was significantly higher in the group B compared to healthy controls (P=0.0014). Even in the presence of similar proportions of NK subsets, the activities of CD56dimCD16+ NK cells measured by CD107a expression were significantly lower both in the group A (P=0.0023) and in the group B (P=0.0127) compared with those of control group. The activities of CD56dimCD16+ NK cells were not different between group A and B. In the case of CD56brightCD16+/- NK cells, CD107a positivity was significantly lower in the group A compared with controls (P=0.0068) and group B (P=0.0465). Conclusions : Our data suggested that cytolytic functions of NK cells were significantly decreased in advanced TN breast cancer patients compared with those of healthy controls despite a similar proportion of NK cell subsets in pB. Citation Format: In Hae Park, Sun-Young Kong, Joo Hyun Kang, Hye Jin Mo, Tae Sik Kim, Keun Seok Lee, Jungsil Ro. Decreased functions of natural killer cells in peripheral blood of advanced triple negative breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-04-14.