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Review
. 2017 Jul;45(3):163-172.
doi: 10.1249/JES.0000000000000114.

Mobilizing Immune Cells With Exercise for Cancer Immunotherapy

Richard J Simpson  1 , Austin B Bigley, Nadia Agha, Patrick J Hanley, Catherine M Bollard
Affiliations
Review

Mobilizing Immune Cells With Exercise for Cancer Immunotherapy

Richard J Simpson et al. Exerc Sport Sci Rev. 2017 Jul.

Abstract

Hematopoietic stem cell (HSC) transplantation and adoptive transfer immunotherapy are effective in treating blood cancers and posttransplant infections, but low-circulating cell numbers in patients and donors are oftentimes a limiting factor. We postulate that a single exercise bout will increase the yield of patient- and donor-derived HSCs and cytotoxic lymphocytes to improve this form of treatment for cancer patients.

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Figures

Figure 1.
Figure 1.
Exercise as an adjuvant for viral specific T-cell (VST) isolation and ex vivo expansion. Successful adoptive transfer of donor-derived VSTs is oftentimes limited by low numbers of circulating VSTs in donor blood. A single bout of exercise mobilizes VSTs into the peripheral circulation, increasing their concentration per unit volume of whole blood. Stimulating whole blood samples with viral peptide pools allows 2–3 times more VSTs to be isolated from the donor during exercise using IFN-γ capture antibodies and magnetic cell sorting for direct transfer to the hematopoietic stem cell transplant (HSCT) patient (Direct Isolation Method). Similarly, isolating and expanding a fixed number of peripheral blood mononuclear cells (PBMCs) from donors after exercise allows 2–5 times more VSTs to be manufactured when co-cultured with viral peptides and growth cytokines over 8–10 days prior to adoptive transfer (ex vivo Expansion Method).
Figure 2.
Figure 2.
Exercise as an adjuvant for CD34+ stem cell mobilization following growth-colony stimulating factor (G-CSF) treatment. A single bout of exercise mobilizes CD34+ stem cells adhered to the vascular endothelium, causing a 2-fold increase in the number of CD34+ stem cells in the main axial flow of the peripheral blood compartment. Peripheral blood stem cell (PBSC) collections by apheresis typically begin when the cell concentration exceeds 10 CD34+ cells/μl following G-CSF therapy. Although exercise alone is unlikely to generate or maintain these cell concentrations for an entire PBSC collection procedure lasting 3–4h, the hemodynamic effects of exercise may act as an adjuvant to increase CD34+ stem cell yields following G-CSF therapy. Exercising healthy donors during apheresis following G-CSF therapy may reduce PBSC collection time and the number of PBSC collection sessions required to achieve target CD34+ stem cell counts, thus reducing donor burden and the need for further pharmaceutical interventions that have known toxicities and potentially debilitating side-effects.
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References

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