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

Br J Cancer. 2012 Sep 25;107(7):1107-15. doi: 10.1038/bjc.2012.362. Epub 2012 Aug 21.

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 (HR=0.17; 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / immunology
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / immunology*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / drug effects
  • Cohort Studies
  • Female
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / immunology*
  • Lung Neoplasms / pathology
  • Male
  • Mesothelioma / drug therapy
  • Mesothelioma / immunology
  • Mesothelioma / pathology
  • Middle Aged
  • Organoplatinum Compounds / administration & dosage
  • T-Lymphocyte Subsets / drug effects*
  • T-Lymphocyte Subsets / immunology*
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Organoplatinum Compounds