Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma

H. Tamura, M. Ishibashi, T. Yamashita, S. Tanosaki, N. Okuyama, A. Kondo, H. Hyodo, E. Shinya, H. Takahashi, Haidong M Dong, K. Tamada, L. Chen, K. Dan, K. Ogata

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Abstract

Tumor-associated B7-H1 molecules inhibit antitumor immunity in some malignancies. We found that B7-H1 expression on patient myeloma cells and human myeloma cell lines (HMCLs) was upregulated by cultivating the cells with autologous stromal cells and the human stromal cell line HS-5. Among major cytokines produced by HS-5 cells, interleukin (IL)-6-induced B7-H1 expression on HMCLs. Moreover, HS-5 cell-mediated B7-H1 expression was downregulated by inhibiting IL-6. B7-H1+ HMCLs were more proliferative and less susceptible to antimyeloma chemotherapy compared with B7-H1-HMCLs. Moreover, the former cells showed higher levels of Bcl-2 and FasL expression than the latter. Finally, B7-H1 molecules on HMCLs induced T-cell apoptosis and anergy of tumor-specific T cells. Consistent with these in vitro observations, patients whose myeloma cells expressed high levels of B7-H1 had higher myeloma cell percentages in the bone marrow (BM) and higher serum lactate dehydrogenase levels compared with other myeloma patients. In addition, B7-H1 expression levels were often upregulated after myeloma patients relapsed or became refractory to therapy. Our data indicate that the BM microenvironment upregulates B7-H1 expression on myeloma cells, which links to the two biological actions of inducing T-cell downregulation and enhancing aggressive myeloma-cell characteristics. Modulating the B7-H1 pathway may be worthwhile in myeloma.

Original languageEnglish (US)
Pages (from-to)464-472
Number of pages9
JournalLeukemia
Volume27
Issue number2
DOIs
StatePublished - Feb 2013

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Stromal Cells
Multiple Myeloma
Bone Marrow
Cell Line
B7 Antigens
T-Lymphocytes
Interleukin-6
Down-Regulation
Neoplasms
L-Lactate Dehydrogenase
Immunity
Up-Regulation
Apoptosis
Cytokines
Drug Therapy
Serum

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Tamura, H., Ishibashi, M., Yamashita, T., Tanosaki, S., Okuyama, N., Kondo, A., ... Ogata, K. (2013). Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma. Leukemia, 27(2), 464-472. https://doi.org/10.1038/leu.2012.213

Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma. / Tamura, H.; Ishibashi, M.; Yamashita, T.; Tanosaki, S.; Okuyama, N.; Kondo, A.; Hyodo, H.; Shinya, E.; Takahashi, H.; Dong, Haidong M; Tamada, K.; Chen, L.; Dan, K.; Ogata, K.

In: Leukemia, Vol. 27, No. 2, 02.2013, p. 464-472.

Research output: Contribution to journalArticle

Tamura, H, Ishibashi, M, Yamashita, T, Tanosaki, S, Okuyama, N, Kondo, A, Hyodo, H, Shinya, E, Takahashi, H, Dong, HM, Tamada, K, Chen, L, Dan, K & Ogata, K 2013, 'Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma', Leukemia, vol. 27, no. 2, pp. 464-472. https://doi.org/10.1038/leu.2012.213
Tamura, H. ; Ishibashi, M. ; Yamashita, T. ; Tanosaki, S. ; Okuyama, N. ; Kondo, A. ; Hyodo, H. ; Shinya, E. ; Takahashi, H. ; Dong, Haidong M ; Tamada, K. ; Chen, L. ; Dan, K. ; Ogata, K. / Marrow stromal cells induce B7-H1 expression on myeloma cells, generating aggressive characteristics in multiple myeloma. In: Leukemia. 2013 ; Vol. 27, No. 2. pp. 464-472.
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AU - Okuyama, N.

AU - Kondo, A.

AU - Hyodo, H.

AU - Shinya, E.

AU - Takahashi, H.

AU - Dong, Haidong M

AU - Tamada, K.

AU - Chen, L.

AU - Dan, K.

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