The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancer
Background: Germline HLA class I molecule supertypes are shown to correlate with response to anti-PD-1 therapy. Here, we investigate the significance of germline HLA-A and HLA-B supertypes in tumour microenvironment of non-small-cell lung cancer. Methods: Totally 278 NSCLC patients were collected re...
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| Format: | Article |
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Elsevier
2023-08-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S240584402306156X |
| _version_ | 1797732913016471552 |
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| author | Ruijiang Lin Xiaohua Chen Fei Su Hongbin Wang Biao Han Yanhui Chen Cuixiang Zhang Minjie Ma |
| author_facet | Ruijiang Lin Xiaohua Chen Fei Su Hongbin Wang Biao Han Yanhui Chen Cuixiang Zhang Minjie Ma |
| author_sort | Ruijiang Lin |
| collection | DOAJ |
| description | Background: Germline HLA class I molecule supertypes are shown to correlate with response to anti-PD-1 therapy. Here, we investigate the significance of germline HLA-A and HLA-B supertypes in tumour microenvironment of non-small-cell lung cancer. Methods: Totally 278 NSCLC patients were collected retrospectively. HLA genotyping was conducted using next-generation sequencing. The evaluation of tumour-infiltrating lymphocytes was performed by multiplex immunohistochemistry assay. Correlations among HLA supertypes, tumour infiltrating lymphocytes, and clinicopathological characteristics were assessed. Results: HLA-A03 and HLA-B62 were the supertypes with the highest proportions, at 69.1% and 52.2%, respectively. HLA-A02 or HLA-B62, but not HLA-A03, associated with higher PD-L1+ tumour and stromal cells levels, CD68+ cells, and CD68+PD-L1+ cells. Patients with both HLA-A02 and HLA-B62 supertypes displayed significantly higher PD-L1+ cells, CD68+ cells, and CD8+ cells levels than patients with other supertypes (P = 0.0301, P = 0.0479, P = 0.0192). These cells collectively constitute a hot but immunosuppressive tumour microenvironment. Accordingly, patients with both HLA-A02 and HLA-B62 supertypes had short progression-free survival after surgery (HR = 2.27, P = 0.0373). Conclusions: The HLA-A02B62 supertype could serve as a possible indicator of poor prognosis in early-stage lung cancer. However, it may also act as a favorable prognostic factor for immunotherapy, given its association with a PD-L1-positive tumour microenvironment. |
| first_indexed | 2024-03-12T12:21:25Z |
| format | Article |
| id | doaj.art-298ed844cfa3441d9384ca5df09f2769 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-03-12T12:21:25Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-298ed844cfa3441d9384ca5df09f27692023-08-30T05:53:12ZengElsevierHeliyon2405-84402023-08-0198e18948The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancerRuijiang Lin0Xiaohua Chen1Fei Su2Hongbin Wang3Biao Han4Yanhui Chen5Cuixiang Zhang6Minjie Ma7Department of Thoracic Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Radiotherapy, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Oncology, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Thoracic Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaDepartment of Thoracic Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, ChinaGenecast Precision Medicine Technology Institute, Beijing, ChinaGenecast Precision Medicine Technology Institute, Beijing, ChinaDepartment of Thoracic Surgery, The First Hospital of Lanzhou University, Lanzhou, Gansu, China; Corresponding author. Department of Thoracic Surgery, The First Hospital of Lanzhou University, Lanzhou, 730000, Gansu, China.Background: Germline HLA class I molecule supertypes are shown to correlate with response to anti-PD-1 therapy. Here, we investigate the significance of germline HLA-A and HLA-B supertypes in tumour microenvironment of non-small-cell lung cancer. Methods: Totally 278 NSCLC patients were collected retrospectively. HLA genotyping was conducted using next-generation sequencing. The evaluation of tumour-infiltrating lymphocytes was performed by multiplex immunohistochemistry assay. Correlations among HLA supertypes, tumour infiltrating lymphocytes, and clinicopathological characteristics were assessed. Results: HLA-A03 and HLA-B62 were the supertypes with the highest proportions, at 69.1% and 52.2%, respectively. HLA-A02 or HLA-B62, but not HLA-A03, associated with higher PD-L1+ tumour and stromal cells levels, CD68+ cells, and CD68+PD-L1+ cells. Patients with both HLA-A02 and HLA-B62 supertypes displayed significantly higher PD-L1+ cells, CD68+ cells, and CD8+ cells levels than patients with other supertypes (P = 0.0301, P = 0.0479, P = 0.0192). These cells collectively constitute a hot but immunosuppressive tumour microenvironment. Accordingly, patients with both HLA-A02 and HLA-B62 supertypes had short progression-free survival after surgery (HR = 2.27, P = 0.0373). Conclusions: The HLA-A02B62 supertype could serve as a possible indicator of poor prognosis in early-stage lung cancer. However, it may also act as a favorable prognostic factor for immunotherapy, given its association with a PD-L1-positive tumour microenvironment.http://www.sciencedirect.com/science/article/pii/S240584402306156XHLA supertypePD-L1TilsPrognosisNSCLC |
| spellingShingle | Ruijiang Lin Xiaohua Chen Fei Su Hongbin Wang Biao Han Yanhui Chen Cuixiang Zhang Minjie Ma The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancer Heliyon HLA supertype PD-L1 Tils Prognosis NSCLC |
| title | The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancer |
| title_full | The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancer |
| title_fullStr | The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancer |
| title_full_unstemmed | The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancer |
| title_short | The germline HLA-A02B62 supertype is associated with a PD-L1-positive tumour immune microenvironment and poor prognosis in stage I lung cancer |
| title_sort | germline hla a02b62 supertype is associated with a pd l1 positive tumour immune microenvironment and poor prognosis in stage i lung cancer |
| topic | HLA supertype PD-L1 Tils Prognosis NSCLC |
| url | http://www.sciencedirect.com/science/article/pii/S240584402306156X |
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