PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer
This study investigates the association of PD-L1 expression and immune cell infiltrates and their impact on clinical outcome, in addition to their overlap with microsatellite instability (MSI), HER2 and ATM molecular subgroups of gastric cancer (GC). PD-L1 membrane expression on tumour cells (TC) an...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-02-01
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| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2018.1544442 |
| _version_ | 1819017120602652672 |
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| author | H. K. Angell J. Lee K-M. Kim K. Kim S-T. Kim S. H. Park W. K. Kang A. Sharpe J. Ogden A. Davenport D. R. Hodgson J. C. Barrett E. Kilgour |
| author_facet | H. K. Angell J. Lee K-M. Kim K. Kim S-T. Kim S. H. Park W. K. Kang A. Sharpe J. Ogden A. Davenport D. R. Hodgson J. C. Barrett E. Kilgour |
| author_sort | H. K. Angell |
| collection | DOAJ |
| description | This study investigates the association of PD-L1 expression and immune cell infiltrates and their impact on clinical outcome, in addition to their overlap with microsatellite instability (MSI), HER2 and ATM molecular subgroups of gastric cancer (GC). PD-L1 membrane expression on tumour cells (TC) and infiltrating immune cells (IC), CD3 + T-lymphocytes, CD8+ cytotoxic T-cells, ATM and HER2 were assessed by immunohistochemistry (IHC) in the ACRG (Asian Cancer Research Group) GC cohort (N = 380). EBV status was determined using in situ hybridization and MSI status was performed using PCR and MLH1 IHC. The PD-L1 segment was associated with increased T-cell infiltrates, while the MSI-high segment was enriched for PD-L1, CD3, and CD8. Multivariate analysis confirmed PD-L1 positivity, high CD3 and high CD8 as independent prognostic factors for both disease-free survival and overall survival (all p < 0.05). Patients with MSI-high tumours had better overall survival by both univariate and multivariate analysis. The ATM-low and HER2-high subgroups differed markedly in their immune profile; the ATM-low subgroups enriched for MSI, PD-L1 positivity and CD8 + T-cells, while the HER2 segment was enriched for MSS, with no enrichment for immune markers. Hence, we demonstrate a molecular profiling approach that can divide GC into four molecular subgroups, namely ATM-low, HER2-high, PD-L1 positive and MSI-high with differing levels of immune infiltrates and prognostic significance which may help to stratify patients for response to targeted therapies. |
| first_indexed | 2024-12-21T02:58:29Z |
| format | Article |
| id | doaj.art-f06aed8bacf74578babaddd7db5a76a4 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-21T02:58:29Z |
| publishDate | 2019-02-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-f06aed8bacf74578babaddd7db5a76a42022-12-21T19:18:16ZengTaylor & Francis GroupOncoImmunology2162-402X2019-02-018210.1080/2162402X.2018.15444421544442PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancerH. K. Angell0J. Lee1K-M. Kim2K. Kim3S-T. Kim4S. H. Park5W. K. Kang6A. Sharpe7J. Ogden8A. Davenport9D. R. Hodgson10J. C. Barrett11E. Kilgour12AstraZenecaSungkyunkwan University School of MedicineSamsung Medical Center, Sungkyunkwan University School of MedicineSungkyunkwan University School of MedicineSungkyunkwan University School of MedicineSungkyunkwan University School of MedicineSungkyunkwan University School of MedicineAstraZenecaAstraZenecaManchester Foundation TrustAstraZenecaAstraZenecaAstraZenecaThis study investigates the association of PD-L1 expression and immune cell infiltrates and their impact on clinical outcome, in addition to their overlap with microsatellite instability (MSI), HER2 and ATM molecular subgroups of gastric cancer (GC). PD-L1 membrane expression on tumour cells (TC) and infiltrating immune cells (IC), CD3 + T-lymphocytes, CD8+ cytotoxic T-cells, ATM and HER2 were assessed by immunohistochemistry (IHC) in the ACRG (Asian Cancer Research Group) GC cohort (N = 380). EBV status was determined using in situ hybridization and MSI status was performed using PCR and MLH1 IHC. The PD-L1 segment was associated with increased T-cell infiltrates, while the MSI-high segment was enriched for PD-L1, CD3, and CD8. Multivariate analysis confirmed PD-L1 positivity, high CD3 and high CD8 as independent prognostic factors for both disease-free survival and overall survival (all p < 0.05). Patients with MSI-high tumours had better overall survival by both univariate and multivariate analysis. The ATM-low and HER2-high subgroups differed markedly in their immune profile; the ATM-low subgroups enriched for MSI, PD-L1 positivity and CD8 + T-cells, while the HER2 segment was enriched for MSS, with no enrichment for immune markers. Hence, we demonstrate a molecular profiling approach that can divide GC into four molecular subgroups, namely ATM-low, HER2-high, PD-L1 positive and MSI-high with differing levels of immune infiltrates and prognostic significance which may help to stratify patients for response to targeted therapies.http://dx.doi.org/10.1080/2162402X.2018.1544442pd-l1immune infiltratesgastric canceratmher2 |
| spellingShingle | H. K. Angell J. Lee K-M. Kim K. Kim S-T. Kim S. H. Park W. K. Kang A. Sharpe J. Ogden A. Davenport D. R. Hodgson J. C. Barrett E. Kilgour PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer OncoImmunology pd-l1 immune infiltrates gastric cancer atm her2 |
| title | PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer |
| title_full | PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer |
| title_fullStr | PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer |
| title_full_unstemmed | PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer |
| title_short | PD-L1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer |
| title_sort | pd l1 and immune infiltrates are differentially expressed in distinct subgroups of gastric cancer |
| topic | pd-l1 immune infiltrates gastric cancer atm her2 |
| url | http://dx.doi.org/10.1080/2162402X.2018.1544442 |
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