Abstract
BACKGROUND: The mTOR inhibitor everolimus used in cancer has immune-modulating effects, potentially contributing to an antitumor response but also leading to pulmonary toxicity. We studied the association of immunological cell subsets with antitumor response and pulmonary toxicity in breast cancer patients treated with everolimus plus exemestane. METHODS: In this exploratory analysis, peripheral blood mononuclear cells (PBMCs) were collected at baseline and 14, 35, 60, and 90 days after start of treatment, and at the moment of pulmonary toxicity. The percentage and absolute number of T-cells, B-cells, NK-cells, monocytes and numerous subtypes were measured in peripheral blood using flow cytometric analysis and were compared using a (paired) t-test. RESULTS: From 20 patients, a total of 89 samples were collected. At baseline, responders versus non-responders had 0.86% versus 0.32% CD4+ effector cells (CD45RA+CD27-) (p = 0.1266) and non-response could be predicted with 0.71 sensitivity and 0.82 specificity. Patients who developed pulmonary toxicity compared to patients without pulmonary toxicity had relatively more NKT-cells at baseline (6.0% versus 1.3%, p = 0.0068, 59 k versus 12 k * 10(9)/l, p = 0.0081) and at the moment of toxicity (5.2% versus 1.2%, p = 0.0106 and 47 k versus 16 k * 10(9)/l, p = 0.0466). Baseline percentage NKT cells predicted pulmonary toxicity with 0.78 sensitivity and 1.0 specificity. CONCLUSIONS: Our results suggest that baseline CD4+ effector cells may be predictive of antitumor responses and baseline NKT cells may be predictive of pulmonary toxicity. These results warrant further validation.
