ArticleOncoimmunology2012
Human melanoma-specific CD8(+) T-cells from metastases are capable of antigen-specific degranulation and cytolysis directly ex vivo.
Article in Oncoimmunology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
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- Review
- Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition).European journal of immunology · 2019Article
- Back from the dead: TIL apoptosis in cancer immune evasion.British journal of cancer · 2018Article
- Identification of Novel HLA-A*0201-Restricted CTL Epitopes in Chinese Vitiligo Patients.Scientific reports · 2016Article
- A Well-Controlled Experimental System to Study Interactions of Cytotoxic T Lymphocytes with Tumor Cells.Frontiers in immunology · 2016Article
- T cell differentiation in chronic infection and cancer: functional adaptation or exhaustion?Nature reviews. Immunology · 2014Article
- Examining the presentation of tumor-associated antigens on peptide-pulsed T2 cells.Oncoimmunology · 2013Article
- Rejuvenated T cells attack old tumors.Oncoimmunology · 2013Article
- Inhibitory Receptor Expression Depends More Dominantly on Differentiation and Activation than "Exhaustion" of Human CD8 T Cells.Frontiers in immunology · 2013Article
- Inefficient boosting of antitumor CD8(+) T cells by dendritic-cell vaccines is rescued by restricting T-cell cytotoxic functions.Oncoimmunology · 2012Article
Corrections and comments
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The relatively low frequencies of tumor Ag-specific T-cells in PBMC and metastases from cancer patients have long precluded the analysis of their direct ex vivo cytolytic capacity. Using a new composite technique that works well with low cell numbers, we aimed at determining the functional competence of melanoma-specific CD8(+) T-cells. A multiparameter flow cytometry based technique was applied to assess the cytolytic function, degranulation and IFNγ production by tumor Ag-specific CD8(+) T-cells from PBMC and tumor-infiltrated lymph nodes (TILN) of melanoma patients. We found strong cytotoxicity by T-cells not only when they were isolated from PBMC but also from TILN. Cytotoxicity was observed against peptide-pulsed target cells and melanoma cells presenting the naturally processed endogenous antigen. However, unlike their PBMC-derived counterparts, T-cells from TILN produced only minimal amounts of IFNγ, while exhibiting similar levels of degranulation, revealing a critical functional dichotomy in metastatic lesions. Our finding of partial functional impairment fits well with the current knowledge that T-cells from cancer metastases are so-called exhausted, a state of T-cell hyporesponsiveness also found in chronic viral infections. The identification of responsible mechanisms in the tumor microenvironment is important for improving cancer therapies.
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Registered trials
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