Renal cancer treatment with recipient lymphocyte infusion enhanced the antitumor effect of nonmyeloablative allogeneic stem cell transplantation

Ario Takeuchi, Masatoshi Eto, Katsunori Tatsugami, Hisakata Yamada, Akira Yokomizo, Masaki Shiota, Momoe Itsumi, Junichi Inokuchi, Keijiro Kiyoshima, Takashi Dejima, Kenjiro Imada, Seiji Naito, Yasunobu Yoshikai

Research output: Contribution to journalArticle

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Abstract

Background: Nonmyeloablative allogeneic stem cell transplantation (SCT) is an option for the treatment of metastatic renal cancer. Mature donor T cells cause graft versus-host disease (GVHD) although they are also the main mediators of the beneficial graft-versus-tumor (GVT) activity associated with this treatment. Hence, the segregation of GVT activity from GVHD is an important challenge in managing the clinical course of treatment. We previously reported a series of studies regarding the allograft tolerance induced by allogeneic spleen cells (with bone marrow cells) and cyclophosphamide in mice. Methods: The aim of the present study was to modify the cyclophosphamide-using cell therapy to reduce the risk of GVHD while preserving the antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma with recipient lymphocyte infusion (RLI). Results: Regarding the in vivo antitumor effect, there was a significant difference between RLI and no lymphocyte infusion after the cyclophosphamide treatment, whereas the histologic findings of the small intestine showed that the cyclophosphamide-using cell therapy with RLI decreased the risk of GVHD as compared with donor lymphocyte infusion. In addition, the acquired immunity against RENCA was clearly observed in RLI-treated mice. Conclusions: Our results show that RLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate GVT effects from GVHD by reducing the risk of GVHD. We considered that this was the first report to provide the evidence of nonmyeloablative allogeneic SCT with RLI for the treatment of renal cell carcinoma which never induce complete chimerism. •The aim of the present study was to modify the cyclophosphamide-using cell therapy to reduce the risk of GVHD while preserving the antitumor activity against RENCA, a murine carcinogen-induced renal cell carcinoma with recipient lymphocyte infusion (RLI).•RLI during cyclophosphamide-using nonmyeloablative cell therapy can dissociate GVT effects from GVHD by reducing the risk of GVHD.•In addition, we showed that serum IFN-γ levels were significantly elevated in animals received RLI and that the origin of producing IFN-γ was host-derived CD4 and CD8 T cells in this model.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalTransplant Immunology
Volume32
Issue number2
DOIs
Publication statusPublished - Mar 1 2015

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Kidney Neoplasms
Stem Cell Transplantation
Graft vs Host Disease
Lymphocytes
Cyclophosphamide
Cell- and Tissue-Based Therapy
Renal Cell Carcinoma
Therapeutics
Transplants
Carcinogens
Neoplasms
Transplantation Tolerance
T-Lymphocytes
Chimerism
Adaptive Immunity
Bone Marrow Cells
Small Intestine
Spleen

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Transplantation

Cite this

Renal cancer treatment with recipient lymphocyte infusion enhanced the antitumor effect of nonmyeloablative allogeneic stem cell transplantation. / Takeuchi, Ario; Eto, Masatoshi; Tatsugami, Katsunori; Yamada, Hisakata; Yokomizo, Akira; Shiota, Masaki; Itsumi, Momoe; Inokuchi, Junichi; Kiyoshima, Keijiro; Dejima, Takashi; Imada, Kenjiro; Naito, Seiji; Yoshikai, Yasunobu.

In: Transplant Immunology, Vol. 32, No. 2, 01.03.2015, p. 131-139.

Research output: Contribution to journalArticle

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AU - Eto, Masatoshi

AU - Tatsugami, Katsunori

AU - Yamada, Hisakata

AU - Yokomizo, Akira

AU - Shiota, Masaki

AU - Itsumi, Momoe

AU - Inokuchi, Junichi

AU - Kiyoshima, Keijiro

AU - Dejima, Takashi

AU - Imada, Kenjiro

AU - Naito, Seiji

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