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Indoleamine-2,3-dioxygenase in an immunotherapy model for Ewing sarcoma
Daniela Max1, Caspar D Kühnöl1, Stefan Burdach2
1University Clinic and Polyclinic for Child and Adolescent Medicine, Martin Luther University Halle-Wittenberg, Halle, Germany.
Background/Aim:
Interleukin-2 (IL2) transgenic Ewing sarcoma cells reduce tumor growth in vivo and in vitro. In the present study we analyzed the expression of immune suppressive indoleamine-2,3-dioxygenase (IDO) in this model.
Materials And Methods:
Expression of IDO was analyzed by polymerase chain reaction. The impact of the cluster of differentiation 137 (CD137)/CD137 ligand (CD137L) co-stimulatory system on expression of IDO and different cytokines was analyzed both in vivo and in vitro.
Results:
Tumors that developed in vivo in the presence of IL2 transgenic tumor cells expressed IDO. The presence of CD137L transgenic tumor cells led to down-regulation of IDO. Further in-vitro analysis of this phenomenon indicated that IDO was expressed in tumor cells as a consequence of interferon-gamma produced by lymphocytes in response to IL2. Depending on the concentration of IL2, stimulation of CD137 increased or reduced cytokine production in lymphocytes.
Conclusion:
Our data indicate that the CD137/CD137L pathway can modulate the immune response against Ewing sarcoma cells.
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