Humoral and cellular immune responses after influenza vaccination in patients with postcancer fatigue

Abstract

The aim of this study was to compare humoral and cellular immune responses to influenza vaccination in cancer survivors with and without severe symptoms of fatigue. Severely fatigued (n = 15) and non-fatigued (n = 12) disease-free cancer survivors were vaccinated against seasonal influenza. Humoral immunity was evaluated at baseline and post-vaccination by a hemagglutination inhibition assay. Cellular immunity was evaluated at baseline and post-vaccination by lymphocyte proliferation and activation assays. Regulatory T cells were measured at baseline by flow cytometry and heat-shock protein 90 alpha levels by ELISA. Comparable humoral immune responses were observed in fatigued and non-fatigued patients, both pre- and post-vaccination. At baseline, fatigued patients showed a significantly diminished cellular proliferation upon virus stimulation with strain H3N2 (1414 ± 1201 counts), and a trend in a similar direction with strain H1N1 (3025 ± 2339 counts), compared to non-fatigued patients (3099 ± 2401 and 5877 ± 4604 counts, respectively). The percentage of regulatory T lymphocytes was significantly increased (4.4 ± 2.1% versus 2.4 ± 0.8%) and significantly lower amounts of interleukin 2 were detected prior to vaccination in fatigued compared to non-fatigued patients (36.3 ± 44.3 pg/ml vs. 94.0 ± 45.4 pg/ml with strain H3N2 and 28.4 ± 44.0 pg/ml versus 74.5 ± 56.1 pg/ml with strain H1N1). Pre-vaccination heat-shock protein 90 alpha concentrations, post-vaccination cellular proliferation, and post-vaccination cytokine concentrations did not differ between both groups. In conclusion, influenza vaccination is favorable for severely fatigued cancer survivors and should be recommended when indicated. However, compared to non-fatigued cancer survivors, fatigued cancer survivors showed several significant differences in immunological reactivity at baseline, which warrants further investigation.

Keywords:

• cancer
• fatigue
• immunity
• influenza
• vaccination

Abbreviations:

• CBT, cognitive behavior therapy
• CIS-fatigue, Checklist Individual Strength fatigue subscale
• HI, hemagglutination-inhibition
• HSP90α, human heat shock protein 90 alpha
• IFN- γ, interferon gamma
• IL-2, interleukin 2
• IL-4, interleukin 4
• IL-5, interleukin 5
• IL-10, interleukin 10
• PBMC, peripheral blood mononuclear cells
• PHA, phytohemagglutinin
• Radboudumc, Radboud University Medical Center
• Treg, regulatory T lymphocytes

Disclosure of Potential Conflicts of Interest

No potential conflicts of interest were disclosed.

Acknowledgments

We thank all patients for participating in this study; all physicians for referring patients; colleagues from the outpatient clinic of Medical Oncology for vaccination and blood collection; colleagues from the Department of Tumor Immunology for assistance with PBMC isolation, experiment performance, and helpful advice.

Funding

This work was supported by Pharmachild [FP7] and Paul Speth Fund.