Post-transplantation malignancy

a cell autonomous mechanism with implications for therapy.

Manikkam Suthanthiran, Minoru Hojo, Mary Maluccio, Daniel J. Boffa, F. L. Luan

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Malignancy is a dreaded complication following organ transplantation. Immunosuppressive therapy-induced impairment of the host immune system is the prevailing hypothesis for the high incidence and aggressive progression of post-transplant neoplasm. We summarize our observations supporting an autonomous cellular mechanism for cyclosporine and tacrolimus associated metastases. Cyclosporine conferred tumor invasiveness by a direct effect on the tumor cells and promoted metastases in T-, B-, and NK cell deficient SCID- beige mice, and anti-TGF-beta antibodies reduced metastases. Tacrolimus, another calcineurin inhibitor widely used in transplantation, induced TGF-beta secretion by tumor cells and promoted metastases in the SCID- beige mice. The immunosuppressive macrolide rapamycin reversed an invasive phenotype to a non-invasive one, reduced circulating levels of TGF-beta1 and prevented tumor growth and metastases in the immocompetant BALB/c mice and in the SCID-beige mice. Our studies, in addition to demonstrating a cell autonomous mechanism for tumor progression, advance TGF-beta blockade as an anti-tumor strategy.

Original languageEnglish
Pages (from-to)369-388
Number of pages20
JournalTransactions of the American Clinical and Climatological Association
Volume120
Publication statusPublished - 1 Dec 2009
Externally publishedYes

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Transplantation
SCID Mice
Neoplasm Metastasis
Neoplasms
Transforming Growth Factor beta
Tacrolimus
Therapeutics
Immunosuppressive Agents
Cyclosporine
Transforming Growth Factor beta1
Macrolides
Organ Transplantation
Sirolimus
Natural Killer Cells
Immune System
B-Lymphocytes
Transplants
Phenotype
Antibodies
Incidence

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Post-transplantation malignancy : a cell autonomous mechanism with implications for therapy. / Suthanthiran, Manikkam; Hojo, Minoru; Maluccio, Mary; Boffa, Daniel J.; Luan, F. L.

In: Transactions of the American Clinical and Climatological Association, Vol. 120, 01.12.2009, p. 369-388.

Research output: Contribution to journalArticle

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