Lack of anti-tumour reactivity despite enhanced numbers of circulating natural killer T cells in two patients with metastatic renal cell carcinoma.

Natural killer T (NK T) cells play a central role as intermediates between innate and adaptive immune responses important to induce anti-tumour reactivity in cancer patients. In two of 14 renal cell carcinoma (RCC) patients, treated with interferon (IFN)-α, we detected significantly enhanced numbers of circulating NK T cells which were typed phenotypically and analysed for anti-tumour reactivity. These NK T cells were T cell receptor (TCR) Vα24/Vβ11(+), 6B11(+) and bound CD1d tetramers.

Autoimmune destruction of skin melanocytes by perilesional T cells from vitiligo patients.

In vitiligo, cytotoxic T cells infiltrating the perilesional margin are suspected to be involved in the pathogenesis of the disease. However, it remains to be elucidated whether these T cells are a cause or a consequence of the depigmentation process. T cells we obtained from perilesional skin biopsies, were significantly enriched for melanocyte antigen recognition, compared with healthy skin-infiltrating T cells, and were reactive to melanocyte antigen-specific stimulation.

In situ visualization of antigen-specific T cells in cryopreserved human tissues.

Tetrameric MHC/peptide complexes are important tools for analyzing antigen-specific T cells. The in situ use of tetrameric MHC/peptide complexes in viable tissue sections has several shortcomings: it does not allow the execution of multiple analyses on one single biopsy, the storage of the biopsies, and the co-staining of the tetramer-positive cells for various intracellular molecules. We have developed a novel approach using overnight pre-labeling of viable human tissues with MHC/peptide tetramers, followed by cryopreservation and labeling of the cryosections.

Infiltration of activated dendritic cells and T cells in renal cell carcinoma following combined cytokine immunotherapy.

Objectives: In a phase I study the feasibility, toxicity and immunological effects of peri-operative cytokine immunotherapy of renal cell carcinoma were studied. Main goals were to determine the maximal tolerable dose and detailed in situ analysis of tumor infiltrates.

Methods: Fifteen patients with renal cell carcinoma, undergoing nephrectomy, received subcutaneous immunotherapy, consisting of low-dose IL-2, IFNalpha and GM-CSF, from day -3 prior, until day +5 following surgery in a dose escalation study.

Tumor regression and autoimmunity after reversal of a functionally tolerant state of self-reactive CD8+ T cells.

Many tumor-associated antigens are derived from nonmutated "self" proteins. T cells infiltrating tumor deposits recognize self-antigens presented by tumor cells and can be expanded in vivo with vaccination. These T cells exist in a functionally tolerant state, as they rarely result in tumor eradication.