Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functions
CD19 chimeric antigen receptor (CAR) T-cells have demonstrated remarkable outcomes in B-cell malignancies. Recently, the novel CD19CAR-T cells incorporated with B-cell costimulatory molecules of CD79A/CD40 demonstrated superior antitumor activity in the B-cell lymphoma model compared with CD28 or 4-...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1064339/full |
| _version_ | 1798015756218138624 |
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| author | Socheatraksmey Ung Socheatraksmey Ung Pongsakorn Choochuen Pongsakorn Choochuen Wannakorn Khopanlert Wannakorn Khopanlert Kajornkiat Maneechai Kajornkiat Maneechai Surasak Sangkhathat Surasak Sangkhathat Seitaro Terakura Jakrawadee Julamanee |
| author_facet | Socheatraksmey Ung Socheatraksmey Ung Pongsakorn Choochuen Pongsakorn Choochuen Wannakorn Khopanlert Wannakorn Khopanlert Kajornkiat Maneechai Kajornkiat Maneechai Surasak Sangkhathat Surasak Sangkhathat Seitaro Terakura Jakrawadee Julamanee |
| author_sort | Socheatraksmey Ung |
| collection | DOAJ |
| description | CD19 chimeric antigen receptor (CAR) T-cells have demonstrated remarkable outcomes in B-cell malignancies. Recently, the novel CD19CAR-T cells incorporated with B-cell costimulatory molecules of CD79A/CD40 demonstrated superior antitumor activity in the B-cell lymphoma model compared with CD28 or 4-1BB. Here, we investigated the intrinsic transcriptional gene underlying the functional advantage of CD19.79A.40z CAR-T cells following CD19 antigen exposure using transcriptome analysis compared to CD28 or 4-1BB. Notably, CD19.79A.40z CAR-T cells up-regulated genes involved in T-cell activation, T-cell proliferation, and NF-κB signaling, whereas down-regulated genes associated with T-cell exhaustion and apoptosis. Interestingly, CD19.79A.40z CAR- and CD19.BBz CAR-T cells were enriched in almost similar pathways. Furthermore, gene set enrichment analysis demonstrated the enrichment of genes, which were previously identified to correlate with T-cell proliferation, interferon signaling pathway, and naïve and memory T-cell signatures, and down-regulated T-cell exhaustion genes in CD79A/CD40, compared with the T-cell costimulatory domain. The CD19.79A.40z CAR-T cells also up-regulated genes related to glycolysis and fatty acid metabolism, which are necessary to drive T-cell proliferation and differentiation compared with conventional CD19CAR-T cells. Our study provides a comprehensive insight into the understanding of gene signatures that potentiates the superior antitumor functions by CD19CAR-T cells incorporated with the CD79A/CD40 costimulatory domain. |
| first_indexed | 2024-04-11T15:38:46Z |
| format | Article |
| id | doaj.art-fe3dee24b473479fa270ca67a58db151 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-11T15:38:46Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-fe3dee24b473479fa270ca67a58db1512022-12-22T04:15:53ZengFrontiers Media S.A.Frontiers in Immunology1664-32242022-11-011310.3389/fimmu.2022.10643391064339Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functionsSocheatraksmey Ung0Socheatraksmey Ung1Pongsakorn Choochuen2Pongsakorn Choochuen3Wannakorn Khopanlert4Wannakorn Khopanlert5Kajornkiat Maneechai6Kajornkiat Maneechai7Surasak Sangkhathat8Surasak Sangkhathat9Seitaro Terakura10Jakrawadee Julamanee11Stem Cell Laboratory, Hematology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandTranslational Medicine Research Center, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandStem Cell Laboratory, Hematology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandStem Cell Laboratory, Hematology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandTranslational Medicine Research Center, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandDepartment of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, JapanStem Cell Laboratory, Hematology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Hat Yai, Songkhla, ThailandCD19 chimeric antigen receptor (CAR) T-cells have demonstrated remarkable outcomes in B-cell malignancies. Recently, the novel CD19CAR-T cells incorporated with B-cell costimulatory molecules of CD79A/CD40 demonstrated superior antitumor activity in the B-cell lymphoma model compared with CD28 or 4-1BB. Here, we investigated the intrinsic transcriptional gene underlying the functional advantage of CD19.79A.40z CAR-T cells following CD19 antigen exposure using transcriptome analysis compared to CD28 or 4-1BB. Notably, CD19.79A.40z CAR-T cells up-regulated genes involved in T-cell activation, T-cell proliferation, and NF-κB signaling, whereas down-regulated genes associated with T-cell exhaustion and apoptosis. Interestingly, CD19.79A.40z CAR- and CD19.BBz CAR-T cells were enriched in almost similar pathways. Furthermore, gene set enrichment analysis demonstrated the enrichment of genes, which were previously identified to correlate with T-cell proliferation, interferon signaling pathway, and naïve and memory T-cell signatures, and down-regulated T-cell exhaustion genes in CD79A/CD40, compared with the T-cell costimulatory domain. The CD19.79A.40z CAR-T cells also up-regulated genes related to glycolysis and fatty acid metabolism, which are necessary to drive T-cell proliferation and differentiation compared with conventional CD19CAR-T cells. Our study provides a comprehensive insight into the understanding of gene signatures that potentiates the superior antitumor functions by CD19CAR-T cells incorporated with the CD79A/CD40 costimulatory domain.https://www.frontiersin.org/articles/10.3389/fimmu.2022.1064339/fullgene expression profilingCAR-T cellCD79A/CD40costimulatory domainCD19 |
| spellingShingle | Socheatraksmey Ung Socheatraksmey Ung Pongsakorn Choochuen Pongsakorn Choochuen Wannakorn Khopanlert Wannakorn Khopanlert Kajornkiat Maneechai Kajornkiat Maneechai Surasak Sangkhathat Surasak Sangkhathat Seitaro Terakura Jakrawadee Julamanee Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functions Frontiers in Immunology gene expression profiling CAR-T cell CD79A/CD40 costimulatory domain CD19 |
| title | Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functions |
| title_full | Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functions |
| title_fullStr | Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functions |
| title_full_unstemmed | Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functions |
| title_short | Enrichment of T-cell proliferation and memory gene signatures of CD79A/CD40 costimulatory domain potentiates CD19CAR-T cell functions |
| title_sort | enrichment of t cell proliferation and memory gene signatures of cd79a cd40 costimulatory domain potentiates cd19car t cell functions |
| topic | gene expression profiling CAR-T cell CD79A/CD40 costimulatory domain CD19 |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2022.1064339/full |
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