Abstracts (complete list) - Wissenschaft Online

Stefanie Gross, Uwe Trefzer, Wolfram Sterry, Peter Walden
Characterization of tumor-specific versus virus-specific tumorinfiltrating
and peripheral blood T cells from melanoma
patients
Successful tumor immunotherapy depends on two aspects. First, the generation of
sufficient numbers of tumor-specific T cells and, second, that these cells finally „do their
job“. In numerous studies it has been shown, that the first part can be achieved now
quite well. Following vaccination, vaccine-specific T cells can be monitored in the blood
of the patients, but the clinical outcome still remains poor. In a few cases T cells have
been monitored within the tumor as well. These cells are different in phenotype and
functional capacity compared to those from the blood. The changes T cells are
undergoing within the tumor microenvironment are still poorly understood, but remain
one of the obstacles for successful immunotherapy.
To address the question, whether or not, the changes T cells are undergoing within the
tumor microenvironment depend on the specificity of the T cells, we evaluated the
phenotypes of tumor-specific tumor-infiltrating T cells (TIL) and peripheral T cells in
melanoma patients in comparison to T cells specific for immunodominant viral antigens.
We used 12 color flow cytometry to analyze Dextramer stained cells ex vivo. In total 76
samples (54 tumors and 22 PBMC) of 49 patiens and 3 healthy donors were analyzed.
Tumor specific (Tyrosinase, Telomerase and gp100) Dextramer positive cells were
compared to virus specific (CMV and EBV) Dextramer positive cells. These cells were
phenotyped for the expression of markers that are indicators for activation,
differentiation and negative regulation.
In the tumor, we found both, tumor-specific and virus-specific T cells. The tumorspecific
T cells are enriched in the tumor compared to the peripheral blood, but still it
seems that non-tumor-specific T cells represent the majority of T cells within the tumor.
However, the tumor specific T cells showed a different expression pattern for the
activation markers CD25 and CD69 and for the negative regulatory markers PD-1 and
CTLA-4 than the virus specific T cells.
From our results it can be concluded that the infiltration of T cells into the tumor does
not depend on their specificity. T cells which do not recognize tumor cells do enter the
tumor and are affected by the tumor associated cytokine milieu.
Nonetheless, some of the phenotypic changes T cells undergo within the tumor
microenvironment seem to depend on the recognition of their cognate epitope on the
tumor cells.