Antitumor T cell responses in bladder cancer are directed against a limited set of antigens and are modulated by regulatory T cells and routine treatment approaches

Thomas Horn, Jessica Grab, Julia Schusdziarra, Sebastian Schmid, Tobias Maurer, Roman Nawroth, Petra Wolf, Maria Pritsch, Jürgen E. Gschwend, Hubert R. Kübler, Philipp Beckhove

Publikation: Beitrag in FachzeitschriftArtikelBegutachtung

23 Zitate (Scopus)

Abstract

Regulatory T cells (Tregs) 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 13 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 (TAAs) was monitored with an interferon-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 epidermal growth factor receptor (EGFR) (UC: 23% and controls: 0%). After depleting Treg, also new york esophageal (NYES)O1 (19 and 0%) and MUC20 (27 and 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, whereas 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. What's new? While effector T cells (Teff) can inhibit the growth of tumors, regulatory T cells (Treg) can suppress this immune response. In this study of urothelial cancer (UC), the authors identified target antigens for these two subsets of T cells. They found Treg's and Teff's that were specific for the same tumor-associated antigens (TAA's), but these cells were rarely found together within individual UC patients. The authors also monitored various aspects of spontaneous Teff-related anti-tumor immunity during treatment.

OriginalspracheEnglisch
Seiten (von - bis)2145-2156
Seitenumfang12
FachzeitschriftInternational Journal of Cancer
Jahrgang133
Ausgabenummer9
DOIs
PublikationsstatusVeröffentlicht - Nov. 2013
Extern publiziertJa

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