Ex vivo staining of metastatic lymph nodes by class I major histocompatibility complex tetramers reveals high numbers of antigen-experienced tumor-specific cytolytic T lymphocytes
| Autor: | Danila Valmori, Pedro Romero, P. Rod Dunbar, Vincenzo Cerundolo, Graham S. Ogg, Jean-Charles Cerottini, Ji-Li Chen, Donata Rimoldi, Mikael J. Pittet, Danielle Liénard |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male Melan-A/MART-1 Protein Conformation Immunology chemical and pharmacologic phenomena tyrosinase Major histocompatibility complex Immunotherapy Adoptive Lymphocytes Tumor-Infiltrating MART-1 Antigen Antigen Antigens Neoplasm melanoma medicine Humans Immunology and Allergy Amino Acid Sequence Lymph node Aged Staining and Labeling biology Monophenol Monooxygenase Melanoma Histocompatibility Antigens Class I hemic and immune systems Articles T lymphocyte Middle Aged medicine.disease Peptide Fragments tumor immunity Neoplasm Proteins CTL medicine.anatomical_structure Lymphatic Metastasis biology.protein Cancer research Female Indicators and Reagents immunotherapy Lymph Ex vivo T-Lymphocytes Cytotoxic |
| Zdroj: | The Journal of Experimental Medicine |
| Popis: | Characterization of cytolytic T lymphocyte (CTL) responses to tumor antigens has been impeded by a lack of direct assays of CTL activity. We have synthesized reagents (“tetramers”) that specifically stain CTLs recognizing melanoma antigens. Tetramer staining of tumor-infiltrated lymph nodes ex vivo revealed high frequencies of tumor-specific CTLs which were antigen-experienced by surface phenotype. In vitro culture of lymph node cells with cytokines resulted in very large expansions of tumor-specific CTLs that were dependent on the presence of tumor cells in the lymph nodes. Tetramer-guided sorting by flow cytometer allowed isolation of melanoma-specific CTLs and confirmation of their specificity and their ability to lyse autologous tumor cells. Our results demonstrate the value of these novel reagents for monitoring tumor-specific CTL responses and for generating CTLs for adoptive immunotherapy. These data also indicate that strong CTL responses to melanoma often occur in vivo, and that the reactive CTLs have substantial proliferative and tumoricidal potential. |
| Databáze: | OpenAIRE |
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