Regulatory T cells (Treg) play a key role in cancer immune escape.
We identified target antigens of spontaneous tumor-specific T cell responses in urothelial carcinoma (UC) and evaluated their modulation by treatment and Treg. We determined Treg target antigens in UC. Fifty-six UC and thirteen control patients were prospectively enrolled. Blood was drawn before and after routine treatment. Changes in Treg frequency were measured by fluorescence cytometry and the T effector cell (Teff) response against a set of nine tumor-associated antigens (TAA) was monitored with an IFN-gamma ELISpot. Antigen specificity of Treg was determined by their increased capacity to inhibit after TAA-specific activation the proliferation of an autologous T cell population. The highest difference in the overall response rate for the total T cell population was observed for EGFR (UC: 23%, controls 0%). After depleting Treg also NYESO1 (19%, 0%) and MUC20 (27%, 0%) were more frequently recognized in UC patients. In metastasized patients the TAA-directed T cell response was augmented by Treg depletion. Tumor resection seemed to diminish Treg suppression of TAA-specific immunity, while chemotherapy had no effect. We demonstrated the existence of TAA-specific Treg in UC, which share antigen specificities with Teff. The coexistence of TAA-specific Treg and Teff was very rare. Treg frequencies in the peripheral blood were not changed by therapy. In summary, we identified potentially immunologically relevant TAA in UC. TAA-specific T cell responses against these antigens are suppressed by Treg. We identified TAA-specific Treg in UC patients, which do not cooccur with TAA-specific Teff.
Written by:
Horn T, Grab J, Schusdziarra J, Schmid S, Maurer T, Nawroth R, Wolf P, Pritsch M, Gschwend JE, Kübler HR, Beckhove P. Are you the author?
Department of Urology, Klinikum rechts der Isar, Technische Universität München, Germany; Translational Immunology Unit, German Cancer Research Center, Heidelberg, Germany.
Reference: Int J Cancer. 2013 Apr 27. Epub ahead of print.
doi: 10.1002/ijc.28233
PubMed Abstract
PMID: 23625723
UroToday.com Investigative Urology Section
