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BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity
To improve response rate of monotherapy of immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)‐related indicators, it is validated that BCAT2 shapes a noninflamed TME in bladder cancer. The outcomes of mu...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015882/ https://www.ncbi.nlm.nih.gov/pubmed/36642843 http://dx.doi.org/10.1002/advs.202207155 |
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author | Cai, Zhiyong Chen, Jinbo Yu, Zhengzheng Li, Huihuang Liu, Zhi Deng, Dingshan Liu, Jinhui Chen, Chunliang Zhang, Chunyu Ou, Zhenyu Chen, Minfeng Hu, Jiao Zu, Xiongbing |
author_facet | Cai, Zhiyong Chen, Jinbo Yu, Zhengzheng Li, Huihuang Liu, Zhi Deng, Dingshan Liu, Jinhui Chen, Chunliang Zhang, Chunyu Ou, Zhenyu Chen, Minfeng Hu, Jiao Zu, Xiongbing |
author_sort | Cai, Zhiyong |
collection | PubMed |
description | To improve response rate of monotherapy of immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)‐related indicators, it is validated that BCAT2 shapes a noninflamed TME in bladder cancer. The outcomes of multiomics indicate that BCAT2 has an inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities of proinflammatory cytokine/chemokine‐related pathways and T‐cell‐chemotaxis pathway. Immunoassays reveal that secretion of CD8(+)T‐cell‐related chemokines keeps a robust negative correlation with BCAT2, generating a decreasing tendency of CD8(+)T cells around BCAT2(+) tumor cells from far to near. Cotreatment of BCAT2 deficiency and anti‐PD‐1 antibody has a synergistic effect in vivo, implying the potential of BCAT2 in combination therapy. Moreover, the value of BCAT2 in predicting efficacy of immunotherapy is validated in multiple immunotherapy cohorts. Together, as a key molecule in TME, BCAT2 is an emerging target in combination with ICB and a biomarker of guiding precision therapy. |
format | Online Article Text |
id | pubmed-10015882 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100158822023-03-16 BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity Cai, Zhiyong Chen, Jinbo Yu, Zhengzheng Li, Huihuang Liu, Zhi Deng, Dingshan Liu, Jinhui Chen, Chunliang Zhang, Chunyu Ou, Zhenyu Chen, Minfeng Hu, Jiao Zu, Xiongbing Adv Sci (Weinh) Research Articles To improve response rate of monotherapy of immune checkpoint blockade (ICB), it is necessary to find an emerging target in combination therapy. Through analyzing tumor microenvironment (TME)‐related indicators, it is validated that BCAT2 shapes a noninflamed TME in bladder cancer. The outcomes of multiomics indicate that BCAT2 has an inhibitory effect on cytotoxic lymphocyte recruitment by restraining activities of proinflammatory cytokine/chemokine‐related pathways and T‐cell‐chemotaxis pathway. Immunoassays reveal that secretion of CD8(+)T‐cell‐related chemokines keeps a robust negative correlation with BCAT2, generating a decreasing tendency of CD8(+)T cells around BCAT2(+) tumor cells from far to near. Cotreatment of BCAT2 deficiency and anti‐PD‐1 antibody has a synergistic effect in vivo, implying the potential of BCAT2 in combination therapy. Moreover, the value of BCAT2 in predicting efficacy of immunotherapy is validated in multiple immunotherapy cohorts. Together, as a key molecule in TME, BCAT2 is an emerging target in combination with ICB and a biomarker of guiding precision therapy. John Wiley and Sons Inc. 2023-01-15 /pmc/articles/PMC10015882/ /pubmed/36642843 http://dx.doi.org/10.1002/advs.202207155 Text en © 2023 The Authors. Advanced Science published by Wiley‐VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Cai, Zhiyong Chen, Jinbo Yu, Zhengzheng Li, Huihuang Liu, Zhi Deng, Dingshan Liu, Jinhui Chen, Chunliang Zhang, Chunyu Ou, Zhenyu Chen, Minfeng Hu, Jiao Zu, Xiongbing BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity |
title | BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity |
title_full | BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity |
title_fullStr | BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity |
title_full_unstemmed | BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity |
title_short | BCAT2 Shapes a Noninflamed Tumor Microenvironment and Induces Resistance to Anti‐PD‐1/PD‐L1 Immunotherapy by Negatively Regulating Proinflammatory Chemokines and Anticancer Immunity |
title_sort | bcat2 shapes a noninflamed tumor microenvironment and induces resistance to anti‐pd‐1/pd‐l1 immunotherapy by negatively regulating proinflammatory chemokines and anticancer immunity |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10015882/ https://www.ncbi.nlm.nih.gov/pubmed/36642843 http://dx.doi.org/10.1002/advs.202207155 |
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