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


CONCLUSIONS
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.
Tumour Immunology Group, School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia 6009, Australia.
M J
MJ
McCoy
R A
RA
Lake
R G
RG
van der Most
I M
IM
Dick
A K
AK
Nowak
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D016176:T-Lymphocyte Subsets / Q000187:drug effects* / Q000276:immunology*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D009944:Organoplatinum Compounds