Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma
Lung adenocarcinoma (LUAD) is the one of the most prevalent and fatal form of malignant tumors worldwide. Recently, immunotherapy is widely used in the treatment of patients with LUAD and has proved to be clinically effective in improve the prognosis of patients. But there still has been a tremendou...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.1003754/full |
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| author | Yang Li Yang Li Gang Peng Chaoying Qin Xiangyu Wang Yue Li Yueran Li Yueran Li |
| author_facet | Yang Li Yang Li Gang Peng Chaoying Qin Xiangyu Wang Yue Li Yueran Li Yueran Li |
| author_sort | Yang Li |
| collection | DOAJ |
| description | Lung adenocarcinoma (LUAD) is the one of the most prevalent and fatal form of malignant tumors worldwide. Recently, immunotherapy is widely used in the treatment of patients with LUAD and has proved to be clinically effective in improve the prognosis of patients. But there still has been a tremendous thrust to further improve the efficacy of immunotherapy in individual patients with LUAD. The suppression of T cells and their effector functions in the tumor microenvironment (TME) of LUAD is one of the primary reasons for the low efficacy of immunotherapy in some patients with LUAD. Therefore, identifying positive regulators of T cell proliferation (TPRs) may offer novel avenues for LUAD immunotherapy. In this study, we comprehensively evaluated the infiltration patterns of TPRs in 1,066 patients with LUAD using unsupervised consensus clustering and identified correlations with genomic and clinicopathological characteristics. Three infiltrating TPR clusters were defined, and a TPR-related risk signature composed of nine TPRs was constructed using least absolute shrinkage and selection operator-Cox regression algorithms to classify the individual TPR infiltration patterns. Cluster 1 exhibited high levels of T cell infiltration and activation of immune-related signaling pathways, whereas cluster 2 was characterized by robust T cell immune infiltration and enrichment of pathways associated with carcinogenic gene sets and tumor immunity. Cluster 3 was characterized as an immune-desert phenotype. Moreover, the TPR signature was confirmed as an independent prognostic biomarker for drug sensitivity in patients with LUAD. In conclusion, the TPR signature may serve as a novel tool for effectively characterizing immune characteristics and evaluating the prognosis of patients with LUAD. |
| first_indexed | 2024-04-12T05:27:49Z |
| format | Article |
| id | doaj.art-3acc36507d36448e946020a4b489c318 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T05:27:49Z |
| publishDate | 2022-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-3acc36507d36448e946020a4b489c3182022-12-22T03:46:13ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-11-011310.3389/fgene.2022.10037541003754Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinomaYang Li0Yang Li1Gang Peng2Chaoying Qin3Xiangyu Wang4Yue Li5Yueran Li6Yueran Li7Department of Laboratory Medicine, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Neurosurgery, Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Laboratory Medicine, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaDepartment of Gynecology, Third Xiangya Hospital, Central South University, Changsha, Hunan, ChinaLung adenocarcinoma (LUAD) is the one of the most prevalent and fatal form of malignant tumors worldwide. Recently, immunotherapy is widely used in the treatment of patients with LUAD and has proved to be clinically effective in improve the prognosis of patients. But there still has been a tremendous thrust to further improve the efficacy of immunotherapy in individual patients with LUAD. The suppression of T cells and their effector functions in the tumor microenvironment (TME) of LUAD is one of the primary reasons for the low efficacy of immunotherapy in some patients with LUAD. Therefore, identifying positive regulators of T cell proliferation (TPRs) may offer novel avenues for LUAD immunotherapy. In this study, we comprehensively evaluated the infiltration patterns of TPRs in 1,066 patients with LUAD using unsupervised consensus clustering and identified correlations with genomic and clinicopathological characteristics. Three infiltrating TPR clusters were defined, and a TPR-related risk signature composed of nine TPRs was constructed using least absolute shrinkage and selection operator-Cox regression algorithms to classify the individual TPR infiltration patterns. Cluster 1 exhibited high levels of T cell infiltration and activation of immune-related signaling pathways, whereas cluster 2 was characterized by robust T cell immune infiltration and enrichment of pathways associated with carcinogenic gene sets and tumor immunity. Cluster 3 was characterized as an immune-desert phenotype. Moreover, the TPR signature was confirmed as an independent prognostic biomarker for drug sensitivity in patients with LUAD. In conclusion, the TPR signature may serve as a novel tool for effectively characterizing immune characteristics and evaluating the prognosis of patients with LUAD.https://www.frontiersin.org/articles/10.3389/fgene.2022.1003754/fulllung adenocarcinomadriver of T cell proliferationtumor microenvironmentprognosisimmune prognostic model |
| spellingShingle | Yang Li Yang Li Gang Peng Chaoying Qin Xiangyu Wang Yue Li Yueran Li Yueran Li Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma Frontiers in Genetics lung adenocarcinoma driver of T cell proliferation tumor microenvironment prognosis immune prognostic model |
| title | Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma |
| title_full | Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma |
| title_fullStr | Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma |
| title_full_unstemmed | Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma |
| title_short | Positive regulators of T cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma |
| title_sort | positive regulators of t cell proliferation as biomarkers for predicting prognosis and characterizing the immune landscape in lung adenocarcinoma |
| topic | lung adenocarcinoma driver of T cell proliferation tumor microenvironment prognosis immune prognostic model |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.1003754/full |
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