A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma
Abstract Background Although some patients with diffuse large B‐cell lymphoma (DLBCL) show a response to immunotherapy, there are still many who do not respond. This suggests that various immune checkpoints are complicatedly intertwined in the composition of the tumor microenvironment of DLBCL. Pati...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.6268 |
| _version_ | 1797361204128120832 |
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| author | Hyunjee Lee Sang Eun Yoon Seok Jin Kim Won Seog Kim Junhun Cho |
| author_facet | Hyunjee Lee Sang Eun Yoon Seok Jin Kim Won Seog Kim Junhun Cho |
| author_sort | Hyunjee Lee |
| collection | DOAJ |
| description | Abstract Background Although some patients with diffuse large B‐cell lymphoma (DLBCL) show a response to immunotherapy, there are still many who do not respond. This suggests that various immune checkpoints are complicatedly intertwined in the composition of the tumor microenvironment of DLBCL. Patients and Methods To comprehensively understand the expression of various immune checkpoint genes in DLBCL, we performed NanoString assay in 98 patients to investigate 579 genes. In addition, we performed immunohistochemistry for LAG‐3 and PD‐L1 to compare the results with expression in NanoString assay. Results As a result of hierarchical clustering of NanoString assay, 98 DLBCLs were classified into three tumor immune microenvironment clusters. Most immune checkpoint genes showed the highest expression in cluster A and the lowest in cluster C. However, the expression of LAG3 was the highest in cluster C and the lowest in cluster A, showing an expression pattern opposite to that of other immune checkpoint genes. In Cluster A, the expression of genes related to T‐cell activity such as CD8A and GZMB was increased. In Cluster C, the expression of genes related to major histocompatibility complex molecules was the highest. Immunohistochemical stains showed modest agreement with the NanoString results but did not help clustering. Conclusion Our results show that the unique expression pattern of LAG3 in DLBCL contrasts with that of other immune checkpoints. We suggest that the combination of anti‐PD‐1/PD‐L1 and anti‐LAG‐3 blockades in the immunotherapy of DLBCL patients can have a synergistic effect, improving the immunotherapy efficacy and outcome in DLBCL patients. |
| first_indexed | 2024-03-08T15:50:35Z |
| format | Article |
| id | doaj.art-4ce3c97660b24e068912b1aa4cba0da8 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-03-08T15:50:35Z |
| publishDate | 2023-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-4ce3c97660b24e068912b1aa4cba0da82024-01-09T05:41:08ZengWileyCancer Medicine2045-76342023-08-011215163591636910.1002/cam4.6268A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphomaHyunjee Lee0Sang Eun Yoon1Seok Jin Kim2Won Seog Kim3Junhun Cho4Department of Pathology Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul South KoreaDivision of Hematology and Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul South KoreaDivision of Hematology and Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul South KoreaDivision of Hematology and Oncology, Department of Medicine Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul South KoreaDepartment of Pathology Samsung Medical Center, Sungkyunkwan University School of Medicine Seoul South KoreaAbstract Background Although some patients with diffuse large B‐cell lymphoma (DLBCL) show a response to immunotherapy, there are still many who do not respond. This suggests that various immune checkpoints are complicatedly intertwined in the composition of the tumor microenvironment of DLBCL. Patients and Methods To comprehensively understand the expression of various immune checkpoint genes in DLBCL, we performed NanoString assay in 98 patients to investigate 579 genes. In addition, we performed immunohistochemistry for LAG‐3 and PD‐L1 to compare the results with expression in NanoString assay. Results As a result of hierarchical clustering of NanoString assay, 98 DLBCLs were classified into three tumor immune microenvironment clusters. Most immune checkpoint genes showed the highest expression in cluster A and the lowest in cluster C. However, the expression of LAG3 was the highest in cluster C and the lowest in cluster A, showing an expression pattern opposite to that of other immune checkpoint genes. In Cluster A, the expression of genes related to T‐cell activity such as CD8A and GZMB was increased. In Cluster C, the expression of genes related to major histocompatibility complex molecules was the highest. Immunohistochemical stains showed modest agreement with the NanoString results but did not help clustering. Conclusion Our results show that the unique expression pattern of LAG3 in DLBCL contrasts with that of other immune checkpoints. We suggest that the combination of anti‐PD‐1/PD‐L1 and anti‐LAG‐3 blockades in the immunotherapy of DLBCL patients can have a synergistic effect, improving the immunotherapy efficacy and outcome in DLBCL patients.https://doi.org/10.1002/cam4.6268CD274diffuse large B‐cell lymphomaimmune checkpointLAG3LAG‐3PD‐L1 |
| spellingShingle | Hyunjee Lee Sang Eun Yoon Seok Jin Kim Won Seog Kim Junhun Cho A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma Cancer Medicine CD274 diffuse large B‐cell lymphoma immune checkpoint LAG3 LAG‐3 PD‐L1 |
| title | A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma |
| title_full | A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma |
| title_fullStr | A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma |
| title_full_unstemmed | A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma |
| title_short | A unique expression pattern of LAG3 distinct from that of other immune checkpoints in diffuse large B‐cell lymphoma |
| title_sort | unique expression pattern of lag3 distinct from that of other immune checkpoints in diffuse large b cell lymphoma |
| topic | CD274 diffuse large B‐cell lymphoma immune checkpoint LAG3 LAG‐3 PD‐L1 |
| url | https://doi.org/10.1002/cam4.6268 |
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