Publication

Exhaustion of tumor-specific CD8(+) T cells in metastases from melanoma patients

Bart Deplancke, Pedro Romero, Sunil Kumar Raghav, Nathalie Rufer, Lukas Baitsch
2011
Journal Articles

Abstract

In chronic viral infections, CD8(+) T cells become functionally deficient and display multiple molecular alterations. In contrast, only little is known of self- and tumor-specific CD8(+) T cells from mice and humans. Here we determined molecular profiles of tumor-specific CD8(+) T cells from melanoma patients. In peripheral blood from patients vaccinated with CpG and the melanoma antigen Melan-A/MART-1 peptide, we found functional effector T cell populations, with only small but nevertheless significant differences in T cells specific for persistent herpesviruses (EBV and CMV). In contrast, Melan-A/MART-1-specific T cells isolated from metastases from patients with melanoma expressed a large variety of genes associated with T cell exhaustion. The identified exhaustion profile revealed extended molecular alterations. Our data demonstrate a remarkable coexistence of effector cells in circulation and exhausted cells in the tumor environment. Functional T cell impairment is mediated by inhibitory receptors and further molecular pathways, which represent potential targets for cancer therapy.

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https://infoscience.epfl.ch/entities/publication/16ad8341-21ba-4ca8-b1e6-1fe55cbcbd6c

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Bart Deplancke, Pedro Romero, Sunil Kumar Raghav, Nathalie Rufer, Lukas Baitsch
2011
Journal Articles

Abstract

Official source

https://infoscience.epfl.ch/entities/publication/16ad8341-21ba-4ca8-b1e6-1fe55cbcbd6c

About this result

Related concepts (32)

T cell

T cells are one of the important types of white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell surface. T cells are born from hematopoietic stem cells, found in the bone marrow. Developing T cells then migrate to the thymus gland to develop (or mature). T cells derive their name from the thymus. After migration to the thymus, the precursor cells mature into several distinct types of T cells.

Melanoma

Melanoma, also redundantly known as malignant melanoma, is a type of cancer that develops from the pigment-producing cells known as melanocytes. Melanomas typically occur in the skin, but may rarely occur in the mouth, intestines, or eye (uveal melanoma). In women, they most commonly occur on the legs, while in men, they most commonly occur on the back. About 25% of melanomas develop from moles. Changes in a mole that can indicate melanoma include an increase in size, irregular edges, change in color, itchiness, or skin breakdown.

Natural killer cell

Natural killer cells, also known as NK cells or large granular lymphocytes (LGL), are a type of cytotoxic lymphocyte critical to the innate immune system that belong to the rapidly expanding family of known innate lymphoid cells (ILC) and represent 5–20% of all circulating lymphocytes in humans. The role of NK cells is analogous to that of cytotoxic T cells in the vertebrate adaptive immune response. NK cells provide rapid responses to virus-infected cell and other intracellular pathogens acting at around 3 days after infection, and respond to tumor formation.

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