Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors
Cytokine-induced killer (CIK) cells, a heterogeneous T cell population obtained by in vitro differentiation of peripheral blood mononuclear cells (PBMC), represent a promising immunological approach in cancer. Numerous studies have explored the role of CD38, CD39, CD203a/PC-1, and CD73 in generating...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-04-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fphar.2018.00196/full |
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| author | Alberto L. Horenstein Antonella Chillemi Roberta Zini Valeria Quarona Nicoletta Bianchi Rossella Manfredini Roberto Gambari Fabio Malavasi Davide Ferrari |
| author_facet | Alberto L. Horenstein Antonella Chillemi Roberta Zini Valeria Quarona Nicoletta Bianchi Rossella Manfredini Roberto Gambari Fabio Malavasi Davide Ferrari |
| author_sort | Alberto L. Horenstein |
| collection | DOAJ |
| description | Cytokine-induced killer (CIK) cells, a heterogeneous T cell population obtained by in vitro differentiation of peripheral blood mononuclear cells (PBMC), represent a promising immunological approach in cancer. Numerous studies have explored the role of CD38, CD39, CD203a/PC-1, and CD73 in generating extracellular adenosine (ADO) and thus in shaping the tumor niche in favor of proliferation. The findings shown here reveal that CIK cells are able to produce extracellular ADO via traditional (CD39/CD73) and/or alternative (CD38/CD203a/CD73 or CD203a/CD73) pathways. Transcriptome analysis showed the mRNA expression of these molecules and their modulation during PBMC to CIK differentiation. When PBMC from normal subjects or cancer bearing patients were differentiated into CIK cells under normoxic conditions, CD38 and CD39 were greatly up-regulated while the number of CD203a, and CD73 positive cells underwent minor changes. Since hypoxic conditions are often found in tumors, we asked whether CD39, CD38, CD203a, and CD73 expressed by CIK cells were modulated by hypoxia. PBMC isolated from cancer patients and differentiated into CIK cells in hypoxic conditions did not show relevant changes in CD38, CD39, CD73, CD203a, and CD26. CIK cells also expressed A1, A2A, and A2B ADO receptors and they only underwent minor changes as a consequence of hypoxia. The present study sheds light on a previously unknown functional aspect of CIK cells, opening the possibility of pharmacologically modulated ADO-generating ectoezymes to improve CIK cells performance. |
| first_indexed | 2024-12-13T09:43:24Z |
| format | Article |
| id | doaj.art-e5fdd0cfc20d402fb53affd57d29d7da |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-13T09:43:24Z |
| publishDate | 2018-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-e5fdd0cfc20d402fb53affd57d29d7da2022-12-21T23:52:09ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-04-01910.3389/fphar.2018.00196331371Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic ReceptorsAlberto L. Horenstein0Antonella Chillemi1Roberta Zini2Valeria Quarona3Nicoletta Bianchi4Rossella Manfredini5Roberto Gambari6Fabio Malavasi7Davide Ferrari8Laboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Torino, Torino, ItalyLaboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Torino, Torino, ItalyCentre for Regenerative Medicine “Stefano Ferrari,” Department of Life Sciences, University of Modena and Reggio Emilia, Modena, ItalyLaboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Torino, Torino, ItalyDepartment of Life Science and Biotechnology, Section of Microbiology and Applied Pathology, University of Ferrara, Ferrara, ItalyCentre for Regenerative Medicine “Stefano Ferrari,” Department of Life Sciences, University of Modena and Reggio Emilia, Modena, ItalyDepartment of Life Science and Biotechnology, Section of Microbiology and Applied Pathology, University of Ferrara, Ferrara, ItalyLaboratory of Immunogenetics and CeRMS, Department of Medical Sciences, University of Torino, Torino, ItalyDepartment of Life Science and Biotechnology, Section of Microbiology and Applied Pathology, University of Ferrara, Ferrara, ItalyCytokine-induced killer (CIK) cells, a heterogeneous T cell population obtained by in vitro differentiation of peripheral blood mononuclear cells (PBMC), represent a promising immunological approach in cancer. Numerous studies have explored the role of CD38, CD39, CD203a/PC-1, and CD73 in generating extracellular adenosine (ADO) and thus in shaping the tumor niche in favor of proliferation. The findings shown here reveal that CIK cells are able to produce extracellular ADO via traditional (CD39/CD73) and/or alternative (CD38/CD203a/CD73 or CD203a/CD73) pathways. Transcriptome analysis showed the mRNA expression of these molecules and their modulation during PBMC to CIK differentiation. When PBMC from normal subjects or cancer bearing patients were differentiated into CIK cells under normoxic conditions, CD38 and CD39 were greatly up-regulated while the number of CD203a, and CD73 positive cells underwent minor changes. Since hypoxic conditions are often found in tumors, we asked whether CD39, CD38, CD203a, and CD73 expressed by CIK cells were modulated by hypoxia. PBMC isolated from cancer patients and differentiated into CIK cells in hypoxic conditions did not show relevant changes in CD38, CD39, CD73, CD203a, and CD26. CIK cells also expressed A1, A2A, and A2B ADO receptors and they only underwent minor changes as a consequence of hypoxia. The present study sheds light on a previously unknown functional aspect of CIK cells, opening the possibility of pharmacologically modulated ADO-generating ectoezymes to improve CIK cells performance.http://journal.frontiersin.org/article/10.3389/fphar.2018.00196/fullCIKadenosineCD38CD39CD73CD203a/PC-1 |
| spellingShingle | Alberto L. Horenstein Antonella Chillemi Roberta Zini Valeria Quarona Nicoletta Bianchi Rossella Manfredini Roberto Gambari Fabio Malavasi Davide Ferrari Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors Frontiers in Pharmacology CIK adenosine CD38 CD39 CD73 CD203a/PC-1 |
| title | Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors |
| title_full | Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors |
| title_fullStr | Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors |
| title_full_unstemmed | Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors |
| title_short | Cytokine-Induced Killer Cells Express CD39, CD38, CD203a, CD73 Ectoenzymes and P1 Adenosinergic Receptors |
| title_sort | cytokine induced killer cells express cd39 cd38 cd203a cd73 ectoenzymes and p1 adenosinergic receptors |
| topic | CIK adenosine CD38 CD39 CD73 CD203a/PC-1 |
| url | http://journal.frontiersin.org/article/10.3389/fphar.2018.00196/full |
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