CD34+DNAM-1brightCXCR4+ haemopoietic precursors circulate after chemotherapy, seed lung tissue and generate functional innate-like T cells and NK cells
BackgroundThere is little information on the trajectory and developmental fate of Lin-CD34+DNAM-1bright CXCR4+ progenitors exiting bone marrow during systemic inflammation.ObjectiveTo study Lin-CD34+DNAM-1bright CXCR4+ cell circulation in cancer patients, to characterize their entry into involved lu...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-02-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1332781/full |
| _version_ | 1797320948361199616 |
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| author | Carola Perrone Federica Bozzano Maria Giovanna Dal Bello Genny Del Zotto Francesca Antonini Enrico Munari Enrico Maggi Francesca Moretta Alireza Hajabbas Farshchi Gianluca Pariscenti Marco Tagliamento Marco Tagliamento Carlo Genova Carlo Genova Lorenzo Moretta Andrea De Maria Andrea De Maria |
| author_facet | Carola Perrone Federica Bozzano Maria Giovanna Dal Bello Genny Del Zotto Francesca Antonini Enrico Munari Enrico Maggi Francesca Moretta Alireza Hajabbas Farshchi Gianluca Pariscenti Marco Tagliamento Marco Tagliamento Carlo Genova Carlo Genova Lorenzo Moretta Andrea De Maria Andrea De Maria |
| author_sort | Carola Perrone |
| collection | DOAJ |
| description | BackgroundThere is little information on the trajectory and developmental fate of Lin-CD34+DNAM-1bright CXCR4+ progenitors exiting bone marrow during systemic inflammation.ObjectiveTo study Lin-CD34+DNAM-1bright CXCR4+ cell circulation in cancer patients, to characterize their entry into involved lung tissue and to characterize their progenies.MethodsFlow cytometric analysis of PBMC from 18 patients with lung cancer on samples collected immediately before the first and the second treatment was performed to study Lin-CD34+DNAM-1bright CXCR4+ precursors. Precursors were purified (>99%) and cultured in vitro from all patients. Paired PBMC and tissue samples from patients undergoing tumor resection were analyzed by flow cytometry to assess tissue entry and compare phenotype and developmental potential of Lin-CD34+DNAM-1bright CXCR4+ cells in both compartments.ResultsSignificant circulation of Lin-CD34+DNAM-1bright CXCR4+ precursors was observed 20d after the first treatment. Precursors express CXC3CR1, CXCR3, CXCR1 consistent with travel towards inflamed tissues. Flowcytometric analysis of lung tissue samples showed precursor presence in all patients in tumor and neighboring uninvolved areas. Successful purification and in vitro culture from both blood and lung tissue generates a minor proportion of maturing NK cells (<10%) and a predominant proportion (>85%) of α/β T-progenies with innate-like phenotype expressing NKG2D,NKp30,DNAM-1. Innate-like maturing T-cells in vitro are cytotoxic, can be triggered via NKR/TCR co-stimulation and display broad spectrum Th1,Th2 and Th1/Th17 cytokine production.ConclusionIn advanced stage lung cancer CD34+DNAM-1brightCXCR4+ inflammatory precursors increase upon treatment, enter involved tissues, generate functional progenies and may thus represent an additional player contributing to immune balance in the highly SDF-1/CXCR4-biased pro-metastatic tumor microenvironment. |
| first_indexed | 2024-03-08T04:51:24Z |
| format | Article |
| id | doaj.art-316e2aa84ab440c69c590ae740ca2724 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-08T04:51:24Z |
| publishDate | 2024-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-316e2aa84ab440c69c590ae740ca27242024-02-08T05:04:04ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-02-011510.3389/fimmu.2024.13327811332781CD34+DNAM-1brightCXCR4+ haemopoietic precursors circulate after chemotherapy, seed lung tissue and generate functional innate-like T cells and NK cellsCarola Perrone0Federica Bozzano1Maria Giovanna Dal Bello2Genny Del Zotto3Francesca Antonini4Enrico Munari5Enrico Maggi6Francesca Moretta7Alireza Hajabbas Farshchi8Gianluca Pariscenti9Marco Tagliamento10Marco Tagliamento11Carlo Genova12Carlo Genova13Lorenzo Moretta14Andrea De Maria15Andrea De Maria16Experimental Immunology Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyLaboratorio Diagnostico di Autoimmunologia, IRCCS Ospedale Policlinico San Martino, Genova, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyIntegrated Department of Services and Laboratories, IRCCS Istituto Giannina Gaslini, Genova, ItalyIntegrated Department of Services and Laboratories, IRCCS Istituto Giannina Gaslini, Genova, ItalyPathology Unit, Department of Molecular and Translational Medicine, University of Brescia, Brescia, ItalyTumor Immunology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, ItalyDepartment of Laboratory Medicine, Istituto di Ricovero e Cura a Carattere Scientifico Sacro Cuore Don Calabria Hospital, Negrar, Verona, ItalyDepartment of Experimental Medicine, University of Genova, Genova, ItalyThoracic Surgery Unit, IRCCS Ospedale Policlinico San Martino, Genova, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy0Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genova, ItalyLung Cancer Unit, IRCCS Ospedale Policlinico San Martino, Genova, Italy0Department of Internal Medicine and Medical Specialties (DiMI), University of Genova, Genova, ItalyTumor Immunology Unit, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy1Department of Health Sciences, University of Genova, Genova, Italy2Infections of Immunocompromised Hosts Unit, Division of Infectious Diseases, IRCCS Ospedale Policlinico San Martino, Genova, ItalyBackgroundThere is little information on the trajectory and developmental fate of Lin-CD34+DNAM-1bright CXCR4+ progenitors exiting bone marrow during systemic inflammation.ObjectiveTo study Lin-CD34+DNAM-1bright CXCR4+ cell circulation in cancer patients, to characterize their entry into involved lung tissue and to characterize their progenies.MethodsFlow cytometric analysis of PBMC from 18 patients with lung cancer on samples collected immediately before the first and the second treatment was performed to study Lin-CD34+DNAM-1bright CXCR4+ precursors. Precursors were purified (>99%) and cultured in vitro from all patients. Paired PBMC and tissue samples from patients undergoing tumor resection were analyzed by flow cytometry to assess tissue entry and compare phenotype and developmental potential of Lin-CD34+DNAM-1bright CXCR4+ cells in both compartments.ResultsSignificant circulation of Lin-CD34+DNAM-1bright CXCR4+ precursors was observed 20d after the first treatment. Precursors express CXC3CR1, CXCR3, CXCR1 consistent with travel towards inflamed tissues. Flowcytometric analysis of lung tissue samples showed precursor presence in all patients in tumor and neighboring uninvolved areas. Successful purification and in vitro culture from both blood and lung tissue generates a minor proportion of maturing NK cells (<10%) and a predominant proportion (>85%) of α/β T-progenies with innate-like phenotype expressing NKG2D,NKp30,DNAM-1. Innate-like maturing T-cells in vitro are cytotoxic, can be triggered via NKR/TCR co-stimulation and display broad spectrum Th1,Th2 and Th1/Th17 cytokine production.ConclusionIn advanced stage lung cancer CD34+DNAM-1brightCXCR4+ inflammatory precursors increase upon treatment, enter involved tissues, generate functional progenies and may thus represent an additional player contributing to immune balance in the highly SDF-1/CXCR4-biased pro-metastatic tumor microenvironment.https://www.frontiersin.org/articles/10.3389/fimmu.2024.1332781/fullCD34+DNAM-1brightCXCR4+CD34NK celllung tumorNSCLCchemotherapy |
| spellingShingle | Carola Perrone Federica Bozzano Maria Giovanna Dal Bello Genny Del Zotto Francesca Antonini Enrico Munari Enrico Maggi Francesca Moretta Alireza Hajabbas Farshchi Gianluca Pariscenti Marco Tagliamento Marco Tagliamento Carlo Genova Carlo Genova Lorenzo Moretta Andrea De Maria Andrea De Maria CD34+DNAM-1brightCXCR4+ haemopoietic precursors circulate after chemotherapy, seed lung tissue and generate functional innate-like T cells and NK cells Frontiers in Immunology CD34+DNAM-1brightCXCR4+ CD34 NK cell lung tumor NSCLC chemotherapy |
| title | CD34+DNAM-1brightCXCR4+ haemopoietic precursors circulate after chemotherapy, seed lung tissue and generate functional innate-like T cells and NK cells |
| title_full | CD34+DNAM-1brightCXCR4+ haemopoietic precursors circulate after chemotherapy, seed lung tissue and generate functional innate-like T cells and NK cells |
| title_fullStr | CD34+DNAM-1brightCXCR4+ haemopoietic precursors circulate after chemotherapy, seed lung tissue and generate functional innate-like T cells and NK cells |
| title_full_unstemmed | CD34+DNAM-1brightCXCR4+ haemopoietic precursors circulate after chemotherapy, seed lung tissue and generate functional innate-like T cells and NK cells |
| title_short | CD34+DNAM-1brightCXCR4+ haemopoietic precursors circulate after chemotherapy, seed lung tissue and generate functional innate-like T cells and NK cells |
| title_sort | cd34 dnam 1brightcxcr4 haemopoietic precursors circulate after chemotherapy seed lung tissue and generate functional innate like t cells and nk cells |
| topic | CD34+DNAM-1brightCXCR4+ CD34 NK cell lung tumor NSCLC chemotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2024.1332781/full |
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