Abstract Book 2010 - CIMT Annual Meeting

032 Zelba | Immune monitoring
NY-ESO-1-specific T cells in long-term melanoma survivors
Henning Zelba 1 , Benjamin Weide 2 , Claus Garbe 3 , Graham Pawelec 1 , Evelyna Derhovanessian 1
1 Department of Internal Medicine II, Section for Transplantation Immunology and Immunohaematology,
University Hospital, Tuebingen, Germany
2 Department of Dermatology, Division of Dermatooncology, University Hospital, Tuebingen, Germany
Immunotherapy has now become a potentially
effective cancer treatment modality for certain
patients. Theoretically any protein expressed abnormally
by the tumour can serve as a target for
antibodies or T cells, and there is an ever-increasing
list of possible antigen targets. However, it
is not clear whether targeting particular antigens
can result in a better clinical outcome than others.
Moreover, non-immunotherapeutic treatments may
also result in the generation of immune responses
against certain of these target antigens, which may
be associated with improved patient survival.
To test this, we are analysing exceptionally longterm
melanoma survivors (LTS) in comparison to
patients with bad prognosis who progressed during
treatment and died within the usual time period.
Patients included those receiving chemotherapy ( e.
g. Dacarbazin, Temodal,…) and Immunotherapy (
e. g. IL-2 injection, ...).
We analysed CD4+ and CD8+ T-cell responses
against the four common melanomaassociated antigens
Melan-A, MAGE-A3, Survivin and NY-ESO-
1. Antigen-specific T-cell responses were detected
using peptide mixtures spanning the whole sequence
of the molecule after one round of in vitro
sensitization for 12 days. Intracellular production
of six different cytokines (IFN-γ, TNF, IL-2, IL-4,
IL-10 and IL-17) was measured simultaneously in
both CD4+ and CD8+ T-cells by 14 colour multiparameter
flow cytometry, allowing analysis of
phenotype and function (TH1, TH2, TH17) at the
single-cell level.
In this way, we have identified NY-SO-1-specific T
cells in 7 of 10 LTS but in only 1 of 6 short-term survivors.
The prevalence of T-cells specific for Melan-
A, MAGE-A3 or Survivin did not differ between LTS
and other patients. Similar results were obtained
in an independent vaccination trial targeting the
above antigens. NY-ESO-1-specific immune responses
were found in 3 of 5 patients with a good
clinical outcome after vaccination, but in only 1 of
7 patients with a poor clinical outcome. MAGE-A3specific
responses were induced in the majority of
patients after vaccination, but there was no difference
between LTS and poor responders.
In all LTS patients, as well as in the patients with
good clinical outcome in the vaccination trial,
CD4+ and CD8+ NY-ESO-1-specific T cells produced
high levels of IFN-γ and TNF. In contrast,
NY-ESO-1-specific T-cells in the two patients with
bad prognosis did not produce any or only small
amounts of these cytokines. Taken together, our
data suggest that NY-ESO-1 is likely to be a promising
target antigen for melanoma patients and
might be a good marker to predict the clinical
outcome of individual patients.
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