Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells
Summary: CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leuk...
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| Language: | English |
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Elsevier
2025-01-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124724014736 |
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| author | Luciana Melo Garcia Achintyan Gangadharan Pinaki Banerjee Ye Li Andy G.X. Zeng Hind Rafei Paul Lin Bijender Kumar Sunil Acharya May Daher Luis Muniz-Feliciano Gary M. Deyter Gabriel Dominguez Jeong Min Park Francia Reyes Silva Ana Karen Nunez Cortes Rafet Basar Nadima Uprety Mayra Shanley Mecit Kaplan Enli Liu Elizabeth J. Shpall Katayoun Rezvani |
| author_facet | Luciana Melo Garcia Achintyan Gangadharan Pinaki Banerjee Ye Li Andy G.X. Zeng Hind Rafei Paul Lin Bijender Kumar Sunil Acharya May Daher Luis Muniz-Feliciano Gary M. Deyter Gabriel Dominguez Jeong Min Park Francia Reyes Silva Ana Karen Nunez Cortes Rafet Basar Nadima Uprety Mayra Shanley Mecit Kaplan Enli Liu Elizabeth J. Shpall Katayoun Rezvani |
| author_sort | Luciana Melo Garcia |
| collection | DOAJ |
| description | Summary: CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226. CRISPR-Cas9 deletion of CD226 led to reduced LFA-1 recruitment, poor synapse formation, and decreased NK cell anti-leukemic activity. Engineering NK cells to express a chimeric antigen receptor targeting the AML antigen CD38 (CAR38) could overcome the need for CD226 to establish strong immune synapses. LFA-1 blockade reduced CAR38 NK cell activity, and this depended on the CD38 expression levels of AML cells. This suggests parallel but potentially cooperative roles for LFA-1 and CAR38 in synapse formation. Our findings suggest that CAR38 NK cells could be an effective therapeutic strategy to overcome CD226-mediated immune evasion in AML. |
| format | Article |
| id | doaj-art-ed441fb6b8e4454e83d5770aaa2111e7 |
| institution | Kabale University |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-ed441fb6b8e4454e83d5770aaa2111e72025-01-05T04:27:55ZengElsevierCell Reports2211-12472025-01-01441115122Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cellsLuciana Melo Garcia0Achintyan Gangadharan1Pinaki Banerjee2Ye Li3Andy G.X. Zeng4Hind Rafei5Paul Lin6Bijender Kumar7Sunil Acharya8May Daher9Luis Muniz-Feliciano10Gary M. Deyter11Gabriel Dominguez12Jeong Min Park13Francia Reyes Silva14Ana Karen Nunez Cortes15Rafet Basar16Nadima Uprety17Mayra Shanley18Mecit Kaplan19Enli Liu20Elizabeth J. Shpall21Katayoun Rezvani22Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Medicine, Université Laval, Quebec City, QC G1V 0A6, Canada; Hematology-Oncology Service, CHU de Québec – Université Laval, Quebec City, QC G1V 0A6, CanadaDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Immunology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA; Cancer Biology PhD Program, University of South Florida, Tampa, FL 33616, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USAPrincess Margaret Cancer Center, University Healthy Network, Toronto, ON M5G 1L7, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, CanadaDepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USADepartment of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Corresponding authorSummary: CD226 plays a vital role in natural killer (NK) cell cytotoxicity, interacting with its ligands CD112 and CD155 to initiate immune synapse formation, primarily through leukocyte function-associated-1 (LFA-1). Our study examined the role of CD226 in NK cell surveillance of acute myeloid leukemia (AML). NK cells in patients with AML had lower expression of CD226. CRISPR-Cas9 deletion of CD226 led to reduced LFA-1 recruitment, poor synapse formation, and decreased NK cell anti-leukemic activity. Engineering NK cells to express a chimeric antigen receptor targeting the AML antigen CD38 (CAR38) could overcome the need for CD226 to establish strong immune synapses. LFA-1 blockade reduced CAR38 NK cell activity, and this depended on the CD38 expression levels of AML cells. This suggests parallel but potentially cooperative roles for LFA-1 and CAR38 in synapse formation. Our findings suggest that CAR38 NK cells could be an effective therapeutic strategy to overcome CD226-mediated immune evasion in AML.http://www.sciencedirect.com/science/article/pii/S2211124724014736CP: ImmunologyCP: Cancer |
| spellingShingle | Luciana Melo Garcia Achintyan Gangadharan Pinaki Banerjee Ye Li Andy G.X. Zeng Hind Rafei Paul Lin Bijender Kumar Sunil Acharya May Daher Luis Muniz-Feliciano Gary M. Deyter Gabriel Dominguez Jeong Min Park Francia Reyes Silva Ana Karen Nunez Cortes Rafet Basar Nadima Uprety Mayra Shanley Mecit Kaplan Enli Liu Elizabeth J. Shpall Katayoun Rezvani Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells Cell Reports CP: Immunology CP: Cancer |
| title | Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells |
| title_full | Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells |
| title_fullStr | Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells |
| title_full_unstemmed | Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells |
| title_short | Overcoming CD226-related immune evasion in acute myeloid leukemia with CD38 CAR-engineered NK cells |
| title_sort | overcoming cd226 related immune evasion in acute myeloid leukemia with cd38 car engineered nk cells |
| topic | CP: Immunology CP: Cancer |
| url | http://www.sciencedirect.com/science/article/pii/S2211124724014736 |
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