Abstract Book 2010 - CIMT Annual Meeting

082 Bonertz | Tumor biology & interaction with the immune system
Antigen-specific Treg in colorectal carcinoma control T cell
responses against a limited tumor antigen repertoire
Andreas Bonertz 1 , Jürgen Weitz 2 , Kim Pietsch 1 , Christoph Schlude 1 , Simone Jünger 1 , Yingzi
Ge 1 , Kashayarsha Khazaie 3 , Moritz Koch 2 , Philipp Beckhove 1
1 Translational Immunology Unit, The German Cancer Research Center, Heidelberg, Germany
2 Department of Visceral Surgery, University Hospital of Heidelberg, Heidelberg, Germany
3 Division of Gastroenterology, Northwestern University Feinberg School of Medicine,
Robert Lurie Comprehensive Cancer Center, Chicago, Illinois, USA
Previous studies suggest that regulatory T cells
(Treg) may suppress a tumor-specific immune
response against established tumors in patients.
Here, we examined how a depletion of Treg influences
the immune reactivity of colorectal carcinoma
(CRC) patients against tumor associated antigens
(TAA) and screened for the specificity of Treg
in the same patients.
We analyzed the T cell (TC) repertoires from the
peripheral blood (PB) of 170 CRC patients for the
presence and frequencies of spontaneously induced
effector/memory TC against synthetic polypeptides
spanning immunogenic regions from 9 different
TAAs (CEA, EGFR, Heparanase, Her2/neu, Mage-3,
Muc-1, p53, Survivin, Telomerase) before and after
depletion of Treg by short-term IFNγ enzyme-linked
immunospot analysis. In comparison, we assayed
PB from 32 healthy donors for the presence of
TAA-specific TC. Patients and healthy donors were
divided into HLA-A2 positive and negative cohorts.
Furthermore, we evaluated for the first time the
specificities of Treg in the same patients for the respective
TAAs. For this, dendritic cells were pulsed
with TAA-peptides or IgG control antigen, coincubated
with autologous Treg and analyzed for the
Treg capacity to suppress in an antigen-dependent
manner the proliferation of polyclonally activated
conventional TC.
In the majority of patients (60%), TAA specific TC
were detected. The TAA recognition pattern was
highly diverse within the CRC patients and was
independent of the patients HLAtype. Healthy individuals
contained significantly less TAA-reactive
TC. After Treg depletion, the proportion of TAAreactive
patients increased to 86%. The strongest
increases of recognition were found for Muc-1 (14%
vs. 39%), EGFR (13% vs. 38%), and CEA (18% vs.
39%), which was also associated with an increase
of the frequencies of TC specific for these antigens.
Treg reacted specifically for individual TAAs in the
PB of 40% of CRC patients.
Treg-induced suppression of proliferation was most
prevalently observed after Treg activation with
Muc-1, HER2/neu, and CEA, whereas Treg specific
for p53 were not observed. Interestingly, specificities
of memory TC and Treg markedly differed
in the majority of patients, leaving the possibility
of using selected sets of TAA for tumor vaccinations
that induce optimal effector TC responses but
minimal Treg activity.
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