LDHA: The Obstacle to T cell responses against tumor
Immunotherapy has become a successful therapeutic strategy in certain solid tumors and hematological malignancies. However, this efficacy of immunotherapy is impeded by limited success rates. Cellular metabolic reprogramming determines the functionality and viability in both cancer cells and immune...
| 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 Oncology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2022.1036477/full |
| _version_ | 1811303566840692736 |
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| author | Yu Tang Shuangshuang Gu Liqun Zhu Yujiao Wu Wei Zhang Chuanxiang Zhao |
| author_facet | Yu Tang Shuangshuang Gu Liqun Zhu Yujiao Wu Wei Zhang Chuanxiang Zhao |
| author_sort | Yu Tang |
| collection | DOAJ |
| description | Immunotherapy has become a successful therapeutic strategy in certain solid tumors and hematological malignancies. However, this efficacy of immunotherapy is impeded by limited success rates. Cellular metabolic reprogramming determines the functionality and viability in both cancer cells and immune cells. Extensive research has unraveled that the limited success of immunotherapy is related to immune evasive metabolic reprogramming in tumor cells and immune cells. As an enzyme that catalyzes the final step of glycolysis, lactate dehydrogenase A (LDHA) has become a major focus of research. Here, we have addressed the structure, localization, and biological features of LDHA. Furthermore, we have discussed the various aspects of epigenetic regulation of LDHA expression, such as histone modification, DNA methylation, N6-methyladenosine (m6A) RNA methylation, and transcriptional control by noncoding RNA. With a focus on the extrinsic (tumor cells) and intrinsic (T cells) functions of LDHA in T-cell responses against tumors, in this article, we have reviewed the current status of LDHA inhibitors and their combination with T cell-mediated immunotherapies and postulated different strategies for future therapeutic regimens. |
| first_indexed | 2024-04-13T07:50:23Z |
| format | Article |
| id | doaj.art-65c1907eae1947dba525c59db909c661 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-04-13T07:50:23Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-65c1907eae1947dba525c59db909c6612022-12-22T02:55:33ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2022-11-011210.3389/fonc.2022.10364771036477LDHA: The Obstacle to T cell responses against tumorYu Tang0Shuangshuang Gu1Liqun Zhu2Yujiao Wu3Wei Zhang4Chuanxiang Zhao5Department of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, ChinaShanghai Institute of Rheumatology, Shanghai Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaDepartment of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, ChinaDepartment of Gastroenterology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, ChinaInstitute of Medical Genetics and Reproductive Immunity, School of Medical Science and Laboratory Medicine, Jiangsu College of Nursing, Huai’an, Jiangsu, ChinaImmunotherapy has become a successful therapeutic strategy in certain solid tumors and hematological malignancies. However, this efficacy of immunotherapy is impeded by limited success rates. Cellular metabolic reprogramming determines the functionality and viability in both cancer cells and immune cells. Extensive research has unraveled that the limited success of immunotherapy is related to immune evasive metabolic reprogramming in tumor cells and immune cells. As an enzyme that catalyzes the final step of glycolysis, lactate dehydrogenase A (LDHA) has become a major focus of research. Here, we have addressed the structure, localization, and biological features of LDHA. Furthermore, we have discussed the various aspects of epigenetic regulation of LDHA expression, such as histone modification, DNA methylation, N6-methyladenosine (m6A) RNA methylation, and transcriptional control by noncoding RNA. With a focus on the extrinsic (tumor cells) and intrinsic (T cells) functions of LDHA in T-cell responses against tumors, in this article, we have reviewed the current status of LDHA inhibitors and their combination with T cell-mediated immunotherapies and postulated different strategies for future therapeutic regimens.https://www.frontiersin.org/articles/10.3389/fonc.2022.1036477/fullLDHAlactateT cell responsestumormetabolic reprogramming |
| spellingShingle | Yu Tang Shuangshuang Gu Liqun Zhu Yujiao Wu Wei Zhang Chuanxiang Zhao LDHA: The Obstacle to T cell responses against tumor Frontiers in Oncology LDHA lactate T cell responses tumor metabolic reprogramming |
| title | LDHA: The Obstacle to T cell responses against tumor |
| title_full | LDHA: The Obstacle to T cell responses against tumor |
| title_fullStr | LDHA: The Obstacle to T cell responses against tumor |
| title_full_unstemmed | LDHA: The Obstacle to T cell responses against tumor |
| title_short | LDHA: The Obstacle to T cell responses against tumor |
| title_sort | ldha the obstacle to t cell responses against tumor |
| topic | LDHA lactate T cell responses tumor metabolic reprogramming |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2022.1036477/full |
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