Characterization of T cell epitopes derived from newly-identified tumor associated antigens and antibody responses to tumor antigens (Figure 1)
Identification of HLA-ligands and T-cell epitopes in SCLC
Subsets of CD4+ and CD8+ T cells, immunosuppressive cell subsets within tumors and in the peripheral blood (Figure 2)
Effect of standard therapies on the immune system of cancer
CD4+ and CD8+ T cell induction during peptide-based vaccination: phenotype and (multi)function (Figures 3 & 4)
Correlation between immune response and clinical course
We are analyzing the effects of single adjuvants and combinations thereof on immune cells.
In vitro effects of TLR ligands and combination thereof on immune cells
Immune monitoring of anti-tumor vaccines applied in combination with various adjuvants
Our laboratory is equipped to provide high quality tools for immune monitoring (Figure 5). We are also interested in developing new antibody panels and assays for addressing the phenotype and function of immune cell subsets.
A new assay based on the detection of conformational changes of integrins after T-cell activation (Figure 6)
Figure 1 (click here to enlarge figure 1)
VITAL assay to assess the cytotoxic potential of tumor antigen specific CD8+ clones against peptide-loaded targets or transfectants expressing the relevant tumor antigen (Polychromatic flow cytometry). Laske et al. Cancer Immunol Res. 2013;190-200
Figure 2 (click here to enlarge figure 2)
Frequency of cells expressing inhibitory checkpoint receptors within non Treg CD4+ T cells or CD8+ T cells within TILs (RCC_T), autologous PBMCs (RCC_P), and age and gender-matched healthy donor PBMCs (HD_P). Mean and SD are shown; * p≤0.05 | ** p≤0.01 | *** p≤0.001). Zelba et al. Cancer Immunol Res 2019, 11:1891-1899
Figure 3 (click here to enlarge figure 3)
Induction of vaccine-specific CD4+ T cells in one patient with prostate carcinoma after peptide-based vaccination (IFN-γ ELISPOT assay with HLA-class II-binding peptides).
Figure 4 (click here to enlarge figure 4)
Polyfunctional analysis of vaccine-specific T cells in a cohort of 18 patients with prostate carcinoma. Bars represent means + 95% CI of specific CD4+ T cells expressing each of the five activation markers or all possible combinations thereof. One example of an intracellular cytokine staining is shown. Schuhmacher et al. Journal Immunother Cancer 2020, Nov 8 (2): e001157
Figure 6 (click here to enlarge figure 6)
Assessment of adhesion properties as a T cell monitoring tool. Following T-cell receptor-mediated stimulation, integrin (LFA-1) activation occurs rapidly through an “inside-out” signaling process which leads to an affinity increase and a clustering of membrane-bound integrins. These can be detected using fluorescent multimers of their ligand ICAM-1 (for detection of antigen-specific CD8+ T cells) or using the monoclonal antibody m24 (for detection of antigen-specific CD4+ and CD8+ T cells).