Cytolytic T-cell response against Epstein-Barr virus in lung cancer patients and healthy subjects

Abstract

Background: This study aimed to examine whether EBV seropositive patients with lung cancer have an altered virus-specific CTL response, as compared to age-matched healthy controls and whether any variation in this response could be attributed to senescence.

Methods: Peripheral blood mononuclear cells from lung cancer patients, age-matched and younger healthy individuals were used to measure EBV-specific CTLs after in vitro amplification with the GLCTLVAML and RYSIFFDYM peptides followed by HLA-multimer staining.

Results: Lung cancer patients and aged-matched controls had significantly lesser EBV-specific CTL than younger healthy individuals. Multimer positive populations from either group did not differ with respect to the percentage of multimer positive CTLs and the intensity of multimer binding.

Conclusions: This study provides evidence that patients with lung cancer exhibit an EBV-specific CTL response equivalent to that of age-matched healthy counterparts. These data warrant the examination of whether young individuals have a more robust anti-tumor response, as is the case with the anti-EBV response.

Figure 1

Proportion of individuals (young healthy, aged healthy and patients) containing an EBV peptide specific tet + CD8 + T cell amongst peripheral blood CD8 T cells.

Figure 2

EBV multimer positive populations from patients, age-matched healthy individuals and healthy younger individuals. MLPC, were stained with test multimers folded with BMLF1.A2 or EBNA3C.A24 labelled with APC (y axis) and control multimers folded with irrelevant HLA-A2 or -A24 peptides labelled with PE (x axis). Each plot represents live CD8 lymphocytes with the multimer positive population indicated in each gate.

Figure 3

Flow cytometric characteristics of circulating anti-EBV specific pCTL from patients, age-matched healthy individuals and healthy younger individuals. (A)Percentage of multimer⁺CD8⁺ T cells inside each positive MLPCs (significance is indicate for comparisons between each group). (B)Mean Fluorescence Index (MFI) of HLA-multimers inside the positive MLPCs for each group.