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(American Journal of Pathology. 1999;155:537-547.)
© 1999 American Society for Investigative Pathology

Regular Articles

Tumor-Associated Transforming Growth Factor-ß and Interleukin-10 Contribute to a Systemic Th2 Immune Phenotype in Pancreatic Carcinoma Patients

Graziella Bellone*, Anna Turletti*, Elisa Artusio*, Katia Mareschi*, Anna Carbone*, Daniela Tibaudi*, Antonio Robecchi{dagger}, Giorgio Emanuelli* and Ulrich Rodeck{ddagger}

From the Departments of Clinical Physiopathology*
and Medical-Surgical Disciplines,{dagger}
University of Torino, Torino, Italy; and the Institute of Molecular Medicine and Department of Dermatology and Cutaneous Biology,{ddagger}
Thomas Jefferson University, Philadelphia, Pennsylvania

In this study, we report coexpression of transforming growth factor-ß (TGF-ß) and interleukin-10 (IL-10) in pancreatic carcinoma tissue associated with significantly elevated levels of both cytokines in the sera of pancreatic carcinoma patients. Using conditioned media (CM) of pancreatic carcinoma cells, we further demonstrate that tumor cell-derived TGF-ß and IL-10 inhibited in an additive fashion both proliferation and the development of Th1-like responses in peripheral blood mononuclear cell (PBMC) preparations derived from normal donors. The antiproliferative and Th1-suppressive activities contained in CM of pancreatic carcinoma cells were due primarily to IL-10 and/or TGF-ß, as shown by the capacity of cytokine-specific neutralizing antibodies to reverse these effects. Finally, as compared to normal controls, PBMC derived from pancreatic carcinoma patients displayed a Th2-like cytokine expression pattern upon activation with either anti-CD3 antibody or Staphylococcus aureus strain Cowan I. Taken together, these results suggest that aberrant production of TGF-ß and IL-10 in pancreatic tumor patients skews T-cell cytokine production patterns in favor of a Th2 immunophenotype.




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