Tumor-directed immune responses in cancer patients. Interactions between immune cells and tumors in cancer patients
Characterization of T-cell epitopes derived from newly-identified tumor associated antigens and antibody responses to tumor antigens (Figures 4 & 5)
Subsets of CD4+ and CD8+ T cells, immunosuppressive cell subsets within tumors (renal cell carcinoma, prostate carcinoma, glioma, colon Ca) in the peripheral blood and within tumor tissues (Figure 1)
Effect of standard therapies on the immune system of cancer patients (radiofrequency ablation, radiotherapy, checkpoint inhibition)
Monitoring of antigen-specific T cells during experimental peptide vaccination against cancer. T cell monitoring platform (Figure 6)
CD4+ and CD8+ T-cell induction during peptide-based vaccination: phenotype and (multi)function (Figures 2 & 3)
Correlation between immune response and clinical course
Assay development: Establish, optimize, standardize and validate a palette of immunoassays as a platform for robust and sensitive immunomonitoring .
Even if incorporating strongly immunogenic antigens, cancer vaccines need to be appropriately sensed by the immune system; this is the role of vaccine adjuvants. Aluminum salts (Alum), which are included in most licensed prophylactic vaccines, preferentially supports antibody formation, and is therefore not the adjuvant of choice for cancer vaccines. GM-CSF is an established adjuvant for cancer vaccine but is relatively weak. Hence, novel adjuvants are needed, like toll-like receptor (TLR)-ligands. We are analyzing the effects of adjuvants on immune cells.
In vitro effects of TLR ligands and combination thereof on immune cells
Immunomonitoring of anti-tumor vaccines applied in combination with various adjuvants
Harmonisation of T-cell assays: international initiative from the Cancer Immunoguiding Program
Proficiency panel program for T-cell assays (ELISPOT, HLA-multimer and intracellular cytokine staining)
New technologies and detection of further immune cells (NK, Tregs, MDSCs, reference samples)
Dissemination of data (workshop program and CIP congress sessions)
Multicytokine production of CD4+ and CD8+ effectors in the peripheral blood (PBMC) or infiltrating the tumor (TIL) of a patient with renal cell carcinoma. T cells producing IL-10 are highlighted in black on IFN-γ+ and/or TNF-α+ effectors (Polychromatic flow cytometry, Attig et al, Cancer Res 2009;69:8412).
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).
Phenotypic characterisation of vaccine induced CD8+ T cells using HLA-multimers and differentiation markers (Polychromatic flow cytometry)
Identification of antigen-specific CD8+ T cells. Production of cytokine (IFN-γ and TNF-α) in primed healthy donor CD8+ T lymphocytes after stimulation with two HLA-A*0201-restricted peptides (Polychromatic flow cytometry)
VITAL assay to assess the cytotoxic potential of tumor antigen specific CD8+ clones against peptide-loaded targets or trasnfectants expressing the relevant tumor antigen (Polychromatic flow cytometry, Laske et al, Cancer Immunol Res. 2013;190-200)