Immune Checkpoints OX40 and OX40L in Small-Cell Lung Cancer: Predict Prognosis and Modulate Immune Microenvironment
BackgroundOX40 and OX40 ligand (OX40L), as essential immune checkpoint (IC) modulators, are highly correlated with cancer immunity regulation as well as tumor microenvironment (TME). Immunotherapy showed outstanding advantages in small-cell lung cancer (SCLC) therapy. However, functions and clinical...
Guardado en:
| Autores principales: | , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Frontiers Media S.A.
2021
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/59e410262d1b481d828723a80de63151 |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:59e410262d1b481d828723a80de63151 |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:59e410262d1b481d828723a80de631512021-11-30T18:40:47ZImmune Checkpoints OX40 and OX40L in Small-Cell Lung Cancer: Predict Prognosis and Modulate Immune Microenvironment2234-943X10.3389/fonc.2021.713853https://doaj.org/article/59e410262d1b481d828723a80de631512021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fonc.2021.713853/fullhttps://doaj.org/toc/2234-943XBackgroundOX40 and OX40 ligand (OX40L), as essential immune checkpoint (IC) modulators, are highly correlated with cancer immunity regulation as well as tumor microenvironment (TME). Immunotherapy showed outstanding advantages in small-cell lung cancer (SCLC) therapy. However, functions and clinical significance of OX40 and OX40L in SCLC were not clear yet.Materials and MethodsSCLC samples of 143 patients were collected for immunohistochemistry (IHC) or whole-exome sequencing (WES). We comprehensively explored the expression and mutation of OX40/OX40L in SCLC, and systematically linked OX40/OX40L with TME.ResultsThe expression of OX40/OX40L on tumor cells and tumor-infiltrating lymphocytes (TILs) was found in the IHC cohort and verified in other cohorts with SCLC tissues and cell lines. The results showed co-expression patterns among OX40/OX40L, other ICs, and T-cell markers. The WES data suggested that OX40/OX40L mutation is rare in SCLC (<5%). Patients with positive OX40 protein expression on TILs showed substantially higher recurrence-free survival than those with negative expression (p=0.009). The external dataset also indicated that high OX40/OX40L expression was correlated with better prognosis [overall survival: OX40, p<0.001; OX40L, p=0.019]. Importantly, activation of immunity and high infiltration of CD4(+) and CD8(+) T cells were observed in the high OX40/OX40L expression group.ConclusionsCollectively, this work highlighted the significance of OX40 and OX40L in prognosis and TME cell infiltration characterization of SCLC. Evaluating the OX40/OX40L-expression levels of individual patients with SCLC might contribute to guiding more precise therapy.Peixin ChenPeixin ChenHao WangHao WangLishu ZhaoLishu ZhaoHaoyue GuoHaoyue GuoLiping ZhangWei ZhangChenglong SunChenglong SunSha ZhaoSha ZhaoWei LiWei LiJun ZhuJun ZhuJia YuJia YuChunyan WuYayi HeYayi HeFrontiers Media S.A.articlesmall cell lung cancerOX40 (CD134)OX40 ligandtumor immune microenvironmentprognosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENFrontiers in Oncology, Vol 11 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
small cell lung cancer OX40 (CD134) OX40 ligand tumor immune microenvironment prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
small cell lung cancer OX40 (CD134) OX40 ligand tumor immune microenvironment prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Peixin Chen Peixin Chen Hao Wang Hao Wang Lishu Zhao Lishu Zhao Haoyue Guo Haoyue Guo Liping Zhang Wei Zhang Chenglong Sun Chenglong Sun Sha Zhao Sha Zhao Wei Li Wei Li Jun Zhu Jun Zhu Jia Yu Jia Yu Chunyan Wu Yayi He Yayi He Immune Checkpoints OX40 and OX40L in Small-Cell Lung Cancer: Predict Prognosis and Modulate Immune Microenvironment |
| description |
BackgroundOX40 and OX40 ligand (OX40L), as essential immune checkpoint (IC) modulators, are highly correlated with cancer immunity regulation as well as tumor microenvironment (TME). Immunotherapy showed outstanding advantages in small-cell lung cancer (SCLC) therapy. However, functions and clinical significance of OX40 and OX40L in SCLC were not clear yet.Materials and MethodsSCLC samples of 143 patients were collected for immunohistochemistry (IHC) or whole-exome sequencing (WES). We comprehensively explored the expression and mutation of OX40/OX40L in SCLC, and systematically linked OX40/OX40L with TME.ResultsThe expression of OX40/OX40L on tumor cells and tumor-infiltrating lymphocytes (TILs) was found in the IHC cohort and verified in other cohorts with SCLC tissues and cell lines. The results showed co-expression patterns among OX40/OX40L, other ICs, and T-cell markers. The WES data suggested that OX40/OX40L mutation is rare in SCLC (<5%). Patients with positive OX40 protein expression on TILs showed substantially higher recurrence-free survival than those with negative expression (p=0.009). The external dataset also indicated that high OX40/OX40L expression was correlated with better prognosis [overall survival: OX40, p<0.001; OX40L, p=0.019]. Importantly, activation of immunity and high infiltration of CD4(+) and CD8(+) T cells were observed in the high OX40/OX40L expression group.ConclusionsCollectively, this work highlighted the significance of OX40 and OX40L in prognosis and TME cell infiltration characterization of SCLC. Evaluating the OX40/OX40L-expression levels of individual patients with SCLC might contribute to guiding more precise therapy. |
| format |
article |
| author |
Peixin Chen Peixin Chen Hao Wang Hao Wang Lishu Zhao Lishu Zhao Haoyue Guo Haoyue Guo Liping Zhang Wei Zhang Chenglong Sun Chenglong Sun Sha Zhao Sha Zhao Wei Li Wei Li Jun Zhu Jun Zhu Jia Yu Jia Yu Chunyan Wu Yayi He Yayi He |
| author_facet |
Peixin Chen Peixin Chen Hao Wang Hao Wang Lishu Zhao Lishu Zhao Haoyue Guo Haoyue Guo Liping Zhang Wei Zhang Chenglong Sun Chenglong Sun Sha Zhao Sha Zhao Wei Li Wei Li Jun Zhu Jun Zhu Jia Yu Jia Yu Chunyan Wu Yayi He Yayi He |
| author_sort |
Peixin Chen |
| title |
Immune Checkpoints OX40 and OX40L in Small-Cell Lung Cancer: Predict Prognosis and Modulate Immune Microenvironment |
| title_short |
Immune Checkpoints OX40 and OX40L in Small-Cell Lung Cancer: Predict Prognosis and Modulate Immune Microenvironment |
| title_full |
Immune Checkpoints OX40 and OX40L in Small-Cell Lung Cancer: Predict Prognosis and Modulate Immune Microenvironment |
| title_fullStr |
Immune Checkpoints OX40 and OX40L in Small-Cell Lung Cancer: Predict Prognosis and Modulate Immune Microenvironment |
| title_full_unstemmed |
Immune Checkpoints OX40 and OX40L in Small-Cell Lung Cancer: Predict Prognosis and Modulate Immune Microenvironment |
| title_sort |
immune checkpoints ox40 and ox40l in small-cell lung cancer: predict prognosis and modulate immune microenvironment |
| publisher |
Frontiers Media S.A. |
| publishDate |
2021 |
| url |
https://doaj.org/article/59e410262d1b481d828723a80de63151 |
| work_keys_str_mv |
AT peixinchen immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT peixinchen immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT haowang immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT haowang immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT lishuzhao immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT lishuzhao immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT haoyueguo immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT haoyueguo immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT lipingzhang immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT weizhang immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT chenglongsun immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT chenglongsun immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT shazhao immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT shazhao immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT weili immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT weili immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT junzhu immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT junzhu immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT jiayu immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT jiayu immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT chunyanwu immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT yayihe immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment AT yayihe immunecheckpointsox40andox40linsmallcelllungcancerpredictprognosisandmodulateimmunemicroenvironment |
| _version_ |
1718406324822212608 |