Tumor-Associated Regulatory T Cells in Non-Small-Cell Lung Cancer: Current Advances and Future Perspectives

Liang, Jiaqi; Bi, Guoshu; Shan, Guangyao; Jin, Xing; Bian, Yunyi; Wang, Qun

doi:10.1155/2022/4355386

Cited by 17 publications

(20 citation statements)

References 105 publications

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“…Besides TEX, other immunosuppressive characteristics are also essential to determine the degree of malignancy of TME, which influences immuno- and chemotherapeutic responses. Studies have shown that Treg, MDSC, and TAM extensively infiltrate advanced NSCLC ( Liang et al, 2022 ). In this study, CuRGcluster C, geneCluster B, and high-CuRGscore subtypes were significantly enriched in infiltrating Treg, MDSC, and TAM.…”

Section: Discussionmentioning

confidence: 99%

Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma

et al. 2023

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Background: T cell exhaustion (TEX) heterogeneity leads to unfavorable immunotherapeutic responses in patients with cancer. Classification of TEX molecular phenotypes is pivotal to overcoming TEX and improving immunotherapies in the clinical setting. Cuproptosis is a novel form of programmed cell death associated with tumor progression. However, the relation between cuproptosis-related genes (CuRGs) and the different TEX phenotypes has not been investigated in lung adenocarcinoma (LUAD).Methods: Unsupervised hierarchical clustering and principal component analysis (PCA) algorithm were performed to determine CuRGs-related molecular subtypes and scores for patients with LUAD. The tumor immune microenvironment (TIME) landscape in these molecular subtypes and scores was estimated using ESTIMATE and ssGSEA algorithms. Furthermore, TEX characteristics and phenotypes were evaluated in distinct molecular subtypes and scores through GSVA and Spearman correlation analysis. Finally, TIDE scores, immunophenoscore, pRRophetic, GSE78220, and IMvigor210 datasets were employed to appraise the distinguishing capacity of CuRGscore in immunotherapy and pharmacotherapy effectiveness.Results: We identified three CuRGclusters, three geneClusters, and CuRGscore based on 1012 LUAD transcriptional profiles from five datasets. Compared with other molecular subtypes, CuRGcluster B, geneCluster C, and low-CuRGscore group with good prognosis presented fewer TEX characteristics, including immunosuppressive cells infiltration and TEX-associated gene signatures, signal pathways, checkpoint genes, transcription and inflammatory factors. These molecular subtypes were also responsive in distinguishing TEX phenotype in the terminal, GZMK+, and OXPHOS- TEX subtypes, but not the TCF7+ TEX subtype. Notably, copper importer and exporter, SLC31A1 and ATP7B, were remarkably associated with four TEX phenotypes and nine checkpoint genes such as PDCD1, CTLA4, HAVCR2, TIGIT, LAG3, IDO1, SIGLEC7, CD274, PDCD1LG2, indicating that cuproptosis was involved in the development of TEX and immunosuppressive environment in patients with LUAD. Moreover, CuRGscore was significantly related to the TIDE score, immunophenoscore, and terminal TEX score (Spearman R = 0.62, p < 0.001) to effectively predict immunotherapy and drug sensitivity in both training and external validation cohorts.Conclusion: Our study demonstrated the extensive effect of cuproptosis on TEX. CuRGs-related molecular subtypes and scores could illuminate the heterogeneity of TEX phenotype as reliable tools in predicting prognosis and directing more effective immunotherapeutic and chemotherapeutic strategies for patients with LUAD.

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Section: Discussionmentioning

confidence: 99%

Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma

et al. 2023

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“…Tumor associated-Tregs are present in multiple tissues of patients with LUAD, including tumors, metastatic lymph nodes, and the peripheral blood, playing a fundamental role in creating an immunosuppressive microenvironment in LUAD [37]. Tumor-resident Tregs may originate from peripheral Treg recruitment, local differentiation from naive T cells, the conversion of conventional T cells, or tissue Treg expansion [38].…”

Section: Discussionmentioning

confidence: 99%

Single-cell profiling reveals the trajectory of FOLR2-expressing tumor-associated macrophages to regulatory T cells in the progression of lung adenocarcinoma

Xiang

Zhang

Shang

et al. 2023

Preprint

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Background An immunosuppressive microenvironment enriched with regulatory CD4+ T lymphocytes (Tregs) facilitates the progression of lung adenocarcinoma (LUAD). This study aimed to investigate the cellular mechanism underlying the formation of the immunosuppressive microenvironment in LUAD. Methods LUAD samples (n = 12) and normal lung samples (n = 3) were obtained from patients with different pathological stages of LUAD. Single-cell RNA sequencing was performed to classify cellular components and analyze the transcriptomes including transcription factors/targets and chemokine ligands/receptors, followed by bioinformatics study such as pseudotime analysis. Results Myeloid cells and T cells were the most abundant cell types in tumors and normal lung tissues, while TAM-FOLR2 and CD4+NR4A3 exhibited sharp increases in invasive adenocarcinoma (IA). The enrichment of TAM-FOLR2 in IA resulted from ARM-RETN transformation and recruitment of dendritic cells (DCs) and other TAMs, as evidenced by temporal trajectories and differential CXCL/CXCR expression profiles versus those in the early stages of tumors. Upregulation of CCL17/19/22 expressions was observed in IA as well as in DCs, along with the significant association of TAM-FOLR2 with DCs. The results of pseudotime analysis suggested that CD4+NR4A3 could potentially convert to CD4+FOXP3, further supported by the high expression of NR4A3 target genes in CD4+FOXP3 cells. Robust expression of MHC-II was observed on TAM-FOLR2 cells. Conclusion In LUAD progression, TAM-FOLR2 cells trigger DCs to secret CCL17/19/22, thereby chemoattracting CD4+NR4A3 and promoting CD4+NR4A3 conversion into CD4+FOXP3 by providing MHC-II. Our study reveals an ARM-RETN/TAM-FOLR2/DCs/CD4+NR4A3/CD4+FOXP3 trajectory in shaping the immune suppressive microenvironment along the pathogenesis of LUAD.

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“…In addition, they can also be divided into cytotoxic T lymphocytes (CTLs), helper T lymphocytes (Th lymphocytes), and Tregs according to their function. [64][65][66] Overall, T lymphocyte classification is highly heterogeneous, and T lymphocyte infiltration plays a significant role in osteosarcoma immunotherapy. Fig.…”

Section: The Immune Microenvironment Of Osteosarcomamentioning

confidence: 99%

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

Tian

Cao

et al. 2023

Bone Res

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Osteosarcoma, with poor survival after metastasis, is considered the most common primary bone cancer in adolescents. Notwithstanding the efforts of researchers, its five-year survival rate has only shown limited improvement, suggesting that existing therapeutic strategies are insufficient to meet clinical needs. Notably, immunotherapy has shown certain advantages over traditional tumor treatments in inhibiting metastasis. Therefore, managing the immune microenvironment in osteosarcoma can provide novel and valuable insight into the multifaceted mechanisms underlying the heterogeneity and progression of the disease. Additionally, given the advances in nanomedicine, there exist many advanced nanoplatforms for enhanced osteosarcoma immunotherapy with satisfactory physiochemical characteristics. Here, we review the classification, characteristics, and functions of the key components of the immune microenvironment in osteosarcoma. This review also emphasizes the application, progress, and prospects of osteosarcoma immunotherapy and discusses several nanomedicine-based options to enhance the efficiency of osteosarcoma treatment. Furthermore, we examine the disadvantages of standard treatments and present future perspectives for osteosarcoma immunotherapy.

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Tumor-Associated Regulatory T Cells in Non-Small-Cell Lung Cancer: Current Advances and Future Perspectives

Cited by 17 publications

References 105 publications

Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma

Cuproptosis-related molecular subtypes direct T cell exhaustion phenotypes and therapeutic strategies for patients with lung adenocarcinoma

Single-cell profiling reveals the trajectory of FOLR2-expressing tumor-associated macrophages to regulatory T cells in the progression of lung adenocarcinoma

Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment

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