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Japanese Journal of Clinical Oncology Advance Access published online on September 20, 2009
Japanese Journal of Clinical Oncology, doi:10.1093/jjco/hyp104
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© The Author (2009). Published by Oxford University Press. All rights reserved

Relationship Between Tumor-infiltrating T Lymphocytes and Clinical Response After Reduced-intensity Allogeneic Hematopoietic Stem Cell Transplantation for Advanced Renal Cell Carcinoma: A Single Center Prospective Study

Ken Ishiyama1, Akiyoshi Takami1, Shioto Suzuki2, Hiroyuki Konaka3, Mikio Namiki3, Akifumi Ooi2 and Shinji Nakao1

1 Division of Cancer Medicine, Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science
2 Division of Cancer Medicine, Department of Molecular and Cellular Pathology, Kanazawa University Graduate School of Medical Science
3 Division of Cancer Medicine, Department of Integrative Cancer Therapy and Urology, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa, Japan

For reprints and all correspondence: Ken Ishiyama, Division of Cancer Medicine, Department of Cellular Transplantation Biology, Kanazawa University Graduate School of Medical Science, 13-1 Takaramachi, Kanazawa, Ishikawa 920-8641, Japan. E-mail: ishiyamak{at}med3.m.kanazawa-u.ac.jp

Received June 22, 2009; accepted July 26, 2009

Objective: Renal cell carcinoma (RCC) is refractory to conventional therapy, including chemotherapy and radiation. However, because RCC is sensitive to cytokine therapy, an immunotherapeutic approach such as hematopoietic stem cell transplantation (HSCT) might lead to a cure. We performed an institutional clinical study of HSCT for refractory RCC patients.

Methods: RCC patients aged 50 years or over, refractory to therapy, were eligible for the study. HSCT was performed after reduced-intensity conditioning. Primary endpoint was defined as the survival at day 100 after HSCT with complete donor chimerism, and secondary endpoint was the effectiveness of HSCT.

Results: Seven patients, provided with written informed consent, were enrolled in the study. Six of the seven patients achieved complete donor chimera at day 30 after HSCT, but one patient received second HSCT because of graft rejection. Four patients achieved a partial response (PR) and stable disease was observed in another patient, but these responses were temporary. The disease of the other two patients became progressive. Autopsy findings revealed an accumulation of CD8+ lymphocytes and degenerative changes in the local RCC lesion in three of six patients who responded clinically. An autopsy of a patient who had obtained a PR revealed lymphocyte involvement with a cytotoxic T cell (CTL) phenotype in the metastasis of RCC.

Conclusions: Our results demonstrate the efficacy of HSCT for RCC and suggest that the graft-versus-tumor effect elicited by CTLs is induced in vivo. HSCT should be further explored as a potential curative treatment for RCC.

Key Words: renal cell carcinoma • hematopoietic stem cell transplantation • cytotoxic T cells • graft-versus-tumor effect


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