Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry
We sought to determine the clinicopathological significance of PD-1, LAG3, and TIM3 in gastric cancer (GC) by examining their expression and immune context. Immunohistochemistry (IHC) for PD-1, TIM3, LAG3, and tumor-infiltrating immune cell (TIIC) markers was performed in 385 stage II/III GCs. Epste...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
|
| Series: | OncoImmunology |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/2162402X.2021.1954761 |
| _version_ | 1818974325843165184 |
|---|---|
| author | Yujun Park An Na Seo Jiwon Koh Soo Kyoung Nam Yoonjin Kwak Sang-Hoon Ahn Do Joong Park Hyung-Ho Kim Hye Seung Lee |
| author_facet | Yujun Park An Na Seo Jiwon Koh Soo Kyoung Nam Yoonjin Kwak Sang-Hoon Ahn Do Joong Park Hyung-Ho Kim Hye Seung Lee |
| author_sort | Yujun Park |
| collection | DOAJ |
| description | We sought to determine the clinicopathological significance of PD-1, LAG3, and TIM3 in gastric cancer (GC) by examining their expression and immune context. Immunohistochemistry (IHC) for PD-1, TIM3, LAG3, and tumor-infiltrating immune cell (TIIC) markers was performed in 385 stage II/III GCs. Epstein-Barr virus (EBV) and microsatellite stability (MSI) testing were performed for molecular classification. Chromogenic multiplex IHC (mIHC) for PD1, TIM3, LAG3, CD3, CD8, FOXP3, CD68, and cytokeratin was performed in 58 of the total samples. PD-1, LAG3, and TIM3 expression in TIICs was observed in 91 (23.6%), 193 (50.1%), and 257 (66.8%) GCs by single IHC, respectively. The expression was associated with EBV+ and MSI-H molecular subtypes (p ≤ 0.001). A positive expression of LAG3 in the invasive margin of the tumor was associated with better prognosis in univariate (p = .020) and multivariate (p = .026) survival analyses. The expression of different immune checkpoint receptors (ICRs) was significantly positively correlated. Dual or triple ICR expression was more frequent in high PD-1 and TIM3 density groups than in low-density groups by mIHC (all p ≤ 0.05). ICRs were mainly expressed in CD3+CD8+ and CD3+CD8− T cells. Fifty-eight GCs were classified into three groups by clustering analysis based on mIHC, and the group with the highest ICR expression in TIICs showed significantly better outcomes in progression-free survival (p = .020). In GC, PD-1, LAG3, and TIM3 expression is positively correlated and associated with better prognosis. Our study provides information for the application of effective immune checkpoint inhibitors against GC. |
| first_indexed | 2024-12-20T15:38:16Z |
| format | Article |
| id | doaj.art-d99e511073da482eaddac6931c08be15 |
| institution | Directory Open Access Journal |
| issn | 2162-402X |
| language | English |
| last_indexed | 2024-12-20T15:38:16Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj.art-d99e511073da482eaddac6931c08be152022-12-21T19:35:19ZengTaylor & Francis GroupOncoImmunology2162-402X2021-01-0110110.1080/2162402X.2021.19547611954761Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistryYujun Park0An Na Seo1Jiwon Koh2Soo Kyoung Nam3Yoonjin Kwak4Sang-Hoon Ahn5Do Joong Park6Hyung-Ho Kim7Hye Seung Lee8Seoul National University College of MedicineSchool of Medicine, Kyungpook National University, Kyungpook National University Chilgok HospitalSeoul National University College of MedicineSeoul National University College of MedicineSeoul National University College of MedicineSeoul National University Bundang HospitalSeoul National University College of MedicineSeoul National University Bundang HospitalSeoul National University College of MedicineWe sought to determine the clinicopathological significance of PD-1, LAG3, and TIM3 in gastric cancer (GC) by examining their expression and immune context. Immunohistochemistry (IHC) for PD-1, TIM3, LAG3, and tumor-infiltrating immune cell (TIIC) markers was performed in 385 stage II/III GCs. Epstein-Barr virus (EBV) and microsatellite stability (MSI) testing were performed for molecular classification. Chromogenic multiplex IHC (mIHC) for PD1, TIM3, LAG3, CD3, CD8, FOXP3, CD68, and cytokeratin was performed in 58 of the total samples. PD-1, LAG3, and TIM3 expression in TIICs was observed in 91 (23.6%), 193 (50.1%), and 257 (66.8%) GCs by single IHC, respectively. The expression was associated with EBV+ and MSI-H molecular subtypes (p ≤ 0.001). A positive expression of LAG3 in the invasive margin of the tumor was associated with better prognosis in univariate (p = .020) and multivariate (p = .026) survival analyses. The expression of different immune checkpoint receptors (ICRs) was significantly positively correlated. Dual or triple ICR expression was more frequent in high PD-1 and TIM3 density groups than in low-density groups by mIHC (all p ≤ 0.05). ICRs were mainly expressed in CD3+CD8+ and CD3+CD8− T cells. Fifty-eight GCs were classified into three groups by clustering analysis based on mIHC, and the group with the highest ICR expression in TIICs showed significantly better outcomes in progression-free survival (p = .020). In GC, PD-1, LAG3, and TIM3 expression is positively correlated and associated with better prognosis. Our study provides information for the application of effective immune checkpoint inhibitors against GC.http://dx.doi.org/10.1080/2162402X.2021.1954761gastric cancerimmune checkpoint receptorimmune contextimmunohistochemistry |
| spellingShingle | Yujun Park An Na Seo Jiwon Koh Soo Kyoung Nam Yoonjin Kwak Sang-Hoon Ahn Do Joong Park Hyung-Ho Kim Hye Seung Lee Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry OncoImmunology gastric cancer immune checkpoint receptor immune context immunohistochemistry |
| title | Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry |
| title_full | Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry |
| title_fullStr | Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry |
| title_full_unstemmed | Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry |
| title_short | Expression of the immune checkpoint receptors PD-1, LAG3, and TIM3 in the immune context of stage II and III gastric cancer by using single and chromogenic multiplex immunohistochemistry |
| title_sort | expression of the immune checkpoint receptors pd 1 lag3 and tim3 in the immune context of stage ii and iii gastric cancer by using single and chromogenic multiplex immunohistochemistry |
| topic | gastric cancer immune checkpoint receptor immune context immunohistochemistry |
| url | http://dx.doi.org/10.1080/2162402X.2021.1954761 |
| work_keys_str_mv | AT yujunpark expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry AT annaseo expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry AT jiwonkoh expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry AT sookyoungnam expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry AT yoonjinkwak expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry AT sanghoonahn expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry AT dojoongpark expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry AT hyunghokim expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry AT hyeseunglee expressionoftheimmunecheckpointreceptorspd1lag3andtim3intheimmunecontextofstageiiandiiigastriccancerbyusingsingleandchromogenicmultipleximmunohistochemistry |