Interleukin-15 administration increases graft-versus-tumor activity in recipients of haploidentical hematopoietic SCT

TY - JOUR

T1 - Interleukin-15 administration increases graft-versus-tumor activity in recipients of haploidentical hematopoietic SCT

AU - Sauter, C. T.

AU - Bailey, C. P.

AU - Panis, M. M.

AU - Biswas, C. S.

AU - Budak-Alpdogan, T.

AU - Durham, A.

AU - Flomenberg, N.

AU - Alpdogan, O.

PY - 2013/9

Y1 - 2013/9

N2 - Utilizing a clinically relevant haploidentical (HI) murine transplant model, lethally irradiated B6D2F1 (H2Kb/d) mice were transplanted with T cell-depleted (TCD) BM from B6CBAF1 (H2Kb/k) mice. We found that administration of IL-15 significantly increases the numbers of CD8+ T and natural killer (NK) cells in spleen and BM after transplantion without GVHD. Graft-versus-tumor (GVT) potency of the graft was evaluated upon tumor challenge using P815 tumor cells (H2d). IL-15 administration without T-cell infusion did not result in any survival improvement. However, IL-15 in combination with very low-dose T-cell infusion (1 × 104) significantly increased GVT activity and improved survival in recipients of HI hematopoietic SCT (HSCT). This effect was observed when IL-15 was given at a later time point, rather than immediately following transplantation. IL-15 administration also specifically increased slow-proliferative CD8+ T-cell proliferation and IFN-γ secretion in CD8+ T cells in recipients of CFSE (carboxyfluorescein succinimidyl ester)-labeled HI T-cell infusion, whereas there was no effect on CD4+ T-cell proliferation, suggesting the critical effect of IL-15 on CD8+ T-cell homeostasis in HI host. We conclude that IL-15 can be used for enhancing antileukemia effect of HI-HSCT, which requires presence of donor-derived T cells.

AB - Utilizing a clinically relevant haploidentical (HI) murine transplant model, lethally irradiated B6D2F1 (H2Kb/d) mice were transplanted with T cell-depleted (TCD) BM from B6CBAF1 (H2Kb/k) mice. We found that administration of IL-15 significantly increases the numbers of CD8+ T and natural killer (NK) cells in spleen and BM after transplantion without GVHD. Graft-versus-tumor (GVT) potency of the graft was evaluated upon tumor challenge using P815 tumor cells (H2d). IL-15 administration without T-cell infusion did not result in any survival improvement. However, IL-15 in combination with very low-dose T-cell infusion (1 × 104) significantly increased GVT activity and improved survival in recipients of HI hematopoietic SCT (HSCT). This effect was observed when IL-15 was given at a later time point, rather than immediately following transplantation. IL-15 administration also specifically increased slow-proliferative CD8+ T-cell proliferation and IFN-γ secretion in CD8+ T cells in recipients of CFSE (carboxyfluorescein succinimidyl ester)-labeled HI T-cell infusion, whereas there was no effect on CD4+ T-cell proliferation, suggesting the critical effect of IL-15 on CD8+ T-cell homeostasis in HI host. We conclude that IL-15 can be used for enhancing antileukemia effect of HI-HSCT, which requires presence of donor-derived T cells.

UR - https://www.scopus.com/pages/publications/84883744422

UR - https://www.scopus.com/pages/publications/84883744422#tab=citedBy

U2 - 10.1038/bmt.2013.47

DO - 10.1038/bmt.2013.47

M3 - Article

C2 - 23624821

SN - 0268-3369

VL - 48

SP - 1237

EP - 1242

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

IS - 9

ER -