Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study
Combination therapy with inhibitors of cytotoxic T lymphocyte-associated protein (CTLA)4 and programmed death (PD)-1 has demonstrated efficacy in cancer patients. However, there is little information on CTLA4 and PD-1 expression levels and their clinical significance across diverse cancers. In this...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2020-09-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.02048/full |
| _version_ | 1818112520258322432 |
|---|---|
| author | Jian-Nan Liu Xiang-Shuo Kong Tao Huang Tao Huang Tao Huang Rui Wang Wang Li Qi-Feng Chen Qi-Feng Chen Qi-Feng Chen |
| author_facet | Jian-Nan Liu Xiang-Shuo Kong Tao Huang Tao Huang Tao Huang Rui Wang Wang Li Qi-Feng Chen Qi-Feng Chen Qi-Feng Chen |
| author_sort | Jian-Nan Liu |
| collection | DOAJ |
| description | Combination therapy with inhibitors of cytotoxic T lymphocyte-associated protein (CTLA)4 and programmed death (PD)-1 has demonstrated efficacy in cancer patients. However, there is little information on CTLA4 and PD-1 expression levels and their clinical significance across diverse cancers. In this study, we addressed this question by analyzing PD-1 and CTLA4 levels in 33 different types of cancer along with their prognostic significance using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia datasets. Liver hepatocellular carcinoma (LIHC) patients receiving cytokine-induced killer cell (CIK) immunotherapy at Sun Yat-sen University cancer center were enrolled for survival analysis. The correlation between PD-1/CTLA4 expression and cancer immunity was also analyzed. The results showed that PD-1 and CTLA4 transcript levels varied across cancer cell lines, with aberrant expression detected in certain cancer types; Kaplan–Meier analysis with the Cox proportional hazards model showed that this was closely related to overall survival in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, acute myeloid leukemialymphoma, uterine corpus endometrial carcinoma, and uveal melanoma in TCGA. High serum PD-1 and CTLA4 levels predicted better survival in LIHC patients receiving CIK therapy. PD-1 and CTLA4 levels were found to be significantly correlated with the degree of tumor cell infiltration using Tumor Immune Estimation Resource, Estimating Relative Subsets of RNA Transcripts, and Estimation of Stromal and immune Cells in Malignant Tumor Tissues Using Expression Data as well as with tumor-infiltrating lymphocyte marker expression; they were also related to tumor mutation burden, microsatellite instability, mismatch repair, and the expression of DNA methyltransferases in some cancer types. Gene set enrichment analysis of 33 cancer types provided further evidence for associations between PD-1/CTLA4 levels and cancer development and immunocyte infiltration. Thus, PD-1 and CTLA4 play important roles in tumorigenesis and tumor immunity and can serve as prognostic biomarkers in different cancer types. |
| first_indexed | 2024-12-11T03:20:14Z |
| format | Article |
| id | doaj.art-1bb19d3e287747e59a54d57226aeb4d7 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T03:20:14Z |
| publishDate | 2020-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-1bb19d3e287747e59a54d57226aeb4d72022-12-22T01:22:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-09-011110.3389/fimmu.2020.02048559777Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer StudyJian-Nan Liu0Xiang-Shuo Kong1Tao Huang2Tao Huang3Tao Huang4Rui Wang5Wang Li6Qi-Feng Chen7Qi-Feng Chen8Qi-Feng Chen9Department of Oncology, Yantai Yuhuangding Hospital, Yantai, ChinaDepartment of Oncology, Yantai Yuhuangding Hospital, Yantai, ChinaDepartment of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, ChinaDepartment of Respiratory Oncology, Fushan District People's Hospital, Yantai, ChinaDepartment of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaDepartment of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, ChinaState Key Laboratory of Oncology in South China, Guangzhou, ChinaCollaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, ChinaCombination therapy with inhibitors of cytotoxic T lymphocyte-associated protein (CTLA)4 and programmed death (PD)-1 has demonstrated efficacy in cancer patients. However, there is little information on CTLA4 and PD-1 expression levels and their clinical significance across diverse cancers. In this study, we addressed this question by analyzing PD-1 and CTLA4 levels in 33 different types of cancer along with their prognostic significance using The Cancer Genome Atlas (TCGA) and Cancer Cell Line Encyclopedia datasets. Liver hepatocellular carcinoma (LIHC) patients receiving cytokine-induced killer cell (CIK) immunotherapy at Sun Yat-sen University cancer center were enrolled for survival analysis. The correlation between PD-1/CTLA4 expression and cancer immunity was also analyzed. The results showed that PD-1 and CTLA4 transcript levels varied across cancer cell lines, with aberrant expression detected in certain cancer types; Kaplan–Meier analysis with the Cox proportional hazards model showed that this was closely related to overall survival in breast invasive carcinoma, glioblastoma multiforme, head and neck squamous cell carcinoma, acute myeloid leukemialymphoma, uterine corpus endometrial carcinoma, and uveal melanoma in TCGA. High serum PD-1 and CTLA4 levels predicted better survival in LIHC patients receiving CIK therapy. PD-1 and CTLA4 levels were found to be significantly correlated with the degree of tumor cell infiltration using Tumor Immune Estimation Resource, Estimating Relative Subsets of RNA Transcripts, and Estimation of Stromal and immune Cells in Malignant Tumor Tissues Using Expression Data as well as with tumor-infiltrating lymphocyte marker expression; they were also related to tumor mutation burden, microsatellite instability, mismatch repair, and the expression of DNA methyltransferases in some cancer types. Gene set enrichment analysis of 33 cancer types provided further evidence for associations between PD-1/CTLA4 levels and cancer development and immunocyte infiltration. Thus, PD-1 and CTLA4 play important roles in tumorigenesis and tumor immunity and can serve as prognostic biomarkers in different cancer types.https://www.frontiersin.org/article/10.3389/fimmu.2020.02048/fullpan-cancerPD-1CTLA4prognostic biomarkercancer immunity |
| spellingShingle | Jian-Nan Liu Xiang-Shuo Kong Tao Huang Tao Huang Tao Huang Rui Wang Wang Li Qi-Feng Chen Qi-Feng Chen Qi-Feng Chen Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study Frontiers in Immunology pan-cancer PD-1 CTLA4 prognostic biomarker cancer immunity |
| title | Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study |
| title_full | Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study |
| title_fullStr | Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study |
| title_full_unstemmed | Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study |
| title_short | Clinical Implications of Aberrant PD-1 and CTLA4 Expression for Cancer Immunity and Prognosis: A Pan-Cancer Study |
| title_sort | clinical implications of aberrant pd 1 and ctla4 expression for cancer immunity and prognosis a pan cancer study |
| topic | pan-cancer PD-1 CTLA4 prognostic biomarker cancer immunity |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.02048/full |
| work_keys_str_mv | AT jiannanliu clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT xiangshuokong clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT taohuang clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT taohuang clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT taohuang clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT ruiwang clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT wangli clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT qifengchen clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT qifengchen clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy AT qifengchen clinicalimplicationsofaberrantpd1andctla4expressionforcancerimmunityandprognosisapancancerstudy |