Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma.
The effects on cell signalling networks upon blockade of cytotoxic T lymphocyte-associated antigen-4 (CTLA4) using the monoclonal antibody tremelimumab were studied in peripheral blood mononuclear cell (PBMC) samples from patients with metastatic melanoma.Findings Intracellular flow cytometry was us...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-09-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2939876?pdf=render |
| _version_ | 1819183199413075968 |
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| author | Begoña Comin-Anduix Hooman Sazegar Thinle Chodon Douglas Matsunaga Jason Jalil Erika von Euw Helena Escuin-Ordinas Robert Balderas Bartosz Chmielowski Jesus Gomez-Navarro Richard C Koya Antoni Ribas |
| author_facet | Begoña Comin-Anduix Hooman Sazegar Thinle Chodon Douglas Matsunaga Jason Jalil Erika von Euw Helena Escuin-Ordinas Robert Balderas Bartosz Chmielowski Jesus Gomez-Navarro Richard C Koya Antoni Ribas |
| author_sort | Begoña Comin-Anduix |
| collection | DOAJ |
| description | The effects on cell signalling networks upon blockade of cytotoxic T lymphocyte-associated antigen-4 (CTLA4) using the monoclonal antibody tremelimumab were studied in peripheral blood mononuclear cell (PBMC) samples from patients with metastatic melanoma.Findings Intracellular flow cytometry was used to detect phosphorylated (p) signaling molecules downstream of the T cell receptor (TCR) and cytokine receptors. PBMC from tremelimumab-treated patients were characterized by increase in pp38, pSTAT1 and pSTAT3, and decrease in pLck, pERK1/2 and pSTAT5 levels. These changes were noted in CD4 and CD8 T lymphocytes but also in CD14 monocytes. A divergent pattern of phosphorylation of Zap70, LAT, Akt and STAT6 was noted in patients with or without an objective tumor response.The administration of the CTLA4-blocking antibody tremelimumab to patients with metastatic melanoma influences signaling networks downstream of the TCR and cytokine receptors both in T cells and monocytes. The strong modulation of signaling networks in monocytes suggests that this cell subset may be involved in clinical responses to CTLA4 blockade.clinicaltrials.gov; Registration numbers NCT00090896 and NCT00471887. |
| first_indexed | 2024-12-22T22:58:14Z |
| format | Article |
| id | doaj.art-d7329642d3d84e15b0ee700bc793b3d5 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-22T22:58:14Z |
| publishDate | 2010-09-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-d7329642d3d84e15b0ee700bc793b3d52022-12-21T18:09:45ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-09-0159e1271110.1371/journal.pone.0012711Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma.Begoña Comin-AnduixHooman SazegarThinle ChodonDouglas MatsunagaJason JalilErika von EuwHelena Escuin-OrdinasRobert BalderasBartosz ChmielowskiJesus Gomez-NavarroRichard C KoyaAntoni RibasThe effects on cell signalling networks upon blockade of cytotoxic T lymphocyte-associated antigen-4 (CTLA4) using the monoclonal antibody tremelimumab were studied in peripheral blood mononuclear cell (PBMC) samples from patients with metastatic melanoma.Findings Intracellular flow cytometry was used to detect phosphorylated (p) signaling molecules downstream of the T cell receptor (TCR) and cytokine receptors. PBMC from tremelimumab-treated patients were characterized by increase in pp38, pSTAT1 and pSTAT3, and decrease in pLck, pERK1/2 and pSTAT5 levels. These changes were noted in CD4 and CD8 T lymphocytes but also in CD14 monocytes. A divergent pattern of phosphorylation of Zap70, LAT, Akt and STAT6 was noted in patients with or without an objective tumor response.The administration of the CTLA4-blocking antibody tremelimumab to patients with metastatic melanoma influences signaling networks downstream of the TCR and cytokine receptors both in T cells and monocytes. The strong modulation of signaling networks in monocytes suggests that this cell subset may be involved in clinical responses to CTLA4 blockade.clinicaltrials.gov; Registration numbers NCT00090896 and NCT00471887.http://europepmc.org/articles/PMC2939876?pdf=render |
| spellingShingle | Begoña Comin-Anduix Hooman Sazegar Thinle Chodon Douglas Matsunaga Jason Jalil Erika von Euw Helena Escuin-Ordinas Robert Balderas Bartosz Chmielowski Jesus Gomez-Navarro Richard C Koya Antoni Ribas Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma. PLoS ONE |
| title | Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma. |
| title_full | Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma. |
| title_fullStr | Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma. |
| title_full_unstemmed | Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma. |
| title_short | Modulation of cell signaling networks after CTLA4 blockade in patients with metastatic melanoma. |
| title_sort | modulation of cell signaling networks after ctla4 blockade in patients with metastatic melanoma |
| url | http://europepmc.org/articles/PMC2939876?pdf=render |
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