Post-chemotherapy T-cell recovery is a marker of improved survival in patients with advanced thoracic malignancies

Abstract

Background: There is increasing interest in combining chemotherapy with immunotherapy. However, the effects of chemotherapy on the human immune system are largely unknown. Methods: Longitudinal changes in peripheral T-cell subsets in 40 patients with malignant mesothelioma (MM) or advanced non-small cell lung cancer (NSCLC) receiving platinum-based chemotherapy were assessed by flow cytometry and evaluated for associations with clinical outcome. Results: Proliferating T cells of all subsets were almost entirely depleted at day 8 following chemotherapy, but rapidly recovered above baseline levels. Regulatory T cells (Treg) were most profoundly depleted at this time point. A greater increase in CD8+ T-cell proliferation following one treatment cycle was associated with improved overall survival in univariate (hazard ratio (HR)0.40; P=0.05) and multivariate (HR0.17; P=0.01) analyses. A greater increase in the ratio of CD8+ T cell to Treg proliferation was also predictive of better prognosis.Conclusion:Chemotherapy potentially provides a favourable environment for the development of anti-tumour immunity through transient Treg depletion and regeneration of the T-cell pool. Change in CD8 + T-cell proliferation after one cycle of chemotherapy may represent a useful prognostic indicator in patients with MM and NSCLC. © 2012 Cancer Research UK All rights reserved.