Th1high in tumor microenvironment is an indicator of poor prognosis for patients with NSCLC

Huang, Jian; Shen, Fu‐Ming; Huang, Haitao; Ling, Chunhua; Zhang, Guangbo

doi:10.18632/oncotarget.14471

Cited by 22 publications

(18 citation statements)

References 34 publications

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“…While examining the possible pro-or anti-tumor roles of each TME cell type is beyond the scope of our holistic TME study, we found it interesting that the 32-cell feature sets consistently included both Th1 and Th2 cells. These two helper T cell subtypes were co-enriched in the same patient clusters, despite being thought to be associated with different processes; that is, Th1 cells induce IFNG expression and anti-tumor effects while Th2 release IL-4 and IL-10, which help allow for tumor-escape [46,47]. Whilst the less immunogenic and less favorably surviving LUAD patients showed elevated enrichment of both Th1 and Th2 cells, this result is in line with a previous study using different methods (e.g., flow cytometry) to show that high levels of Th1 in the TME is associated with worse prognosis in NSCLC [47].…”

Section: Discussionmentioning

confidence: 99%

“…These two helper T cell subtypes were co-enriched in the same patient clusters, despite being thought to be associated with different processes; that is, Th1 cells induce IFNG expression and anti-tumor effects while Th2 release IL-4 and IL-10, which help allow for tumor-escape [46,47]. Whilst the less immunogenic and less favorably surviving LUAD patients showed elevated enrichment of both Th1 and Th2 cells, this result is in line with a previous study using different methods (e.g., flow cytometry) to show that high levels of Th1 in the TME is associated with worse prognosis in NSCLC [47]. Lastly, considering the relative scarcity of studies investigating the clinical differences between Th1 and Th2 cells in different TME contexts [48,49], it is possible that this Th1-Th2 balance could mark an avenue worthy of further prognostic investigation, either alone or while considering potential tumor promoting metabolic pathways previously mentioned.…”

Section: Discussionmentioning

confidence: 99%

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An immunogenic NSCLC microenvironment is associated with favorable survival in lung adenocarcinoma

Givechian¹,

Garner

Benz³

et al. 2019

Oncotarget

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The tumor microenvironment consists of an intricately organized system through which immune cells and cancer cells may communicate to regulate antitumor immunogenicity. To this end, non-small cell lung cancer (NSCLC) has been shown to activate a variety of immunological mechanisms, thereby broadening our understanding of lung cancer immunobiology. However, while recent work has highlighted the importance of NSCLC immunology and prognosis, studies have not yet examined the tumor microenvironment (TME) globally in regards to the survival outcomes between two major NSCLC subtypes: lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). In the present study, we identify an immunogenic tumor microenvironment state in NSCLC that is enriched for the lung adenocarcinoma subtype. By utilizing TME cell enrichment scores and RNA-seq expression data, we show that the inflamed TME is associated with favorable patient survival in lung adenocarcinoma, but this does not hold true for lung squamous cell carcinoma. Moreover, differentially regulated pathways between immune-inflamed and immuneexcluded tumors within LUAD and LUSC were not subtype specific. Instead, immuneinflamed LUSC samples possessed elevated immune checkpoint marker expression when compared to those of the LUAD samples, thereby offering a putative explanation for our prognostic observations. These results shed light on the immunological prognostic effects within lung cancer and may encourage further TME exploration between these two subtypes as the landscape of NSCLC therapy progresses.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

An immunogenic NSCLC microenvironment is associated with favorable survival in lung adenocarcinoma

Givechian¹,

Garner

Benz³

et al. 2019

Oncotarget

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“…Typically, the Th1 response is needed against tumors and viral infections. In the above-mentioned case, the T-cell-inactivating ligand PD-L1 on CD45+CD14+ monocytes/macrophages was more abundant in tumor tissue than in the adjacent nontumor tissues 138 . This observation can be reconciled with at least two possible scenarios.…”

Section: Intracellular and Extracellular Cancer Processesmentioning

confidence: 80%

“…In NSCLC specimens, discrete zones of Th2, Th17, and Th1 were found. These zones distinguished the tumor nest from the tumor boundary, adjacent normal lung tissue, or corresponding lymph node tissue 138 . IL-17 activates STAT3 and induces EMT in lung cancer cells in vitro .…”

Section: Intracellular and Extracellular Cancer Processesmentioning

confidence: 99%

Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode

Vlahopoulos

2017

Cancer Biology & Medicine

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The role of the transcription factor NF-κB in shaping the cancer microenvironment is becoming increasingly clear. Inflammation alters the activity of enzymes that modulate NF-κB function, and causes extensive changes in genomic chromatin that ultimately drastically alter cell-specific gene expression. NF-κB regulates the expression of cytokines and adhesion factors that control interactions among adjacent cells. As such, NF-κB fine tunes tissue cellular composition, as well as tissues' interactions with the immune system. Therefore, NF-κB changes the cell response to hormones and to contact with neighboring cells. Activating NF-κB confers transcriptional and phenotypic plasticity to a cell and thereby enables profound local changes in tissue function and composition. Research suggests that the regulation of NF-κB target genes is specifically altered in cancer. Such alterations occur not only due to mutations of NF-κB regulatory proteins, but also because of changes in the activity of specific proteostatic modules and metabolic pathways. This article describes the molecular mode of NF-κB regulation with a few characteristic examples of target genes.

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“…Although most of the evidence supports that patients with more infiltrating Th1 cells exhibit a good prognosis, there is also research that indicates that patients with more infiltrating Th1 cells suffer a poorer prognosis compared with those with fewer Th1 cells, as evaluated by flow cytometry. The data from that study indicated that the IFN-γ secreted by Th1 cells could enhance the PD-L1 signal in macrophages and tumor cells [ 36 ]. Even though the Th1 and Th2 status was estimated from the bulk RNA sequencing indirectly, the information suggests that the roles of T helper cells in the tumor microenvironment are more complicated and merit further investigation.…”

Section: Discussionmentioning

confidence: 99%

A high-risk luminal A dominant breast cancer subtype with increased mobility

Guo

Chen

Zhang

et al. 2019

Breast Cancer Res Treat

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Purpose Breast cancer is a heterogeneous disease, and although advances in molecular subtyping have been achieved in recent years, most subtyping strategies target individual genes independent of one another and primarily concentrate on proliferative markers. The contributions of biological processes and immune patterns have been neglected in breast cancer subtype stratification. Methods We performed a gene set variation analysis to simplify the information on biological processes using hallmark terms and to decompose immune cell data using the immune cell gene terms on 985 breast invasive ductal/lobular carcinoma RNAseq samples in the TCGA database. Results The samples were gathered into three clusters following implementation of the t-SNE and DBSCAN algorithms and were categorized as ‘hallmark-tsne’ subtypes. Here, we identified a high-risk luminal A dominant breast cancer subtype (C3) that displayed increased motility, cancer stem cell-like features, a higher expression of hormone/luminal-related genes, a lower expression of proliferation-related genes and immune dysfunction. With regard to immune dysfunction, we observed that the motility-increased C3 subtype exhibited high granulocyte colony stimulating factor (G-CSF) expression accompanied by neutrophil aggregation. Cancer cells that produce high levels of G-CSF can stimulate neutrophils to form neutrophil extracellular traps, which promote cancer cell migration. This finding sheds light on one potential explanation for why the C3 subtype correlates with poor prognosis. Conclusions The hallmark-tsne subtypes confirmed again that even the luminal A subtype is heterogeneous and can be further subdivided. The biological processes and immune heterogeneity of breast cancer must be understood to facilitate the improvement of clinical treatments. Electronic supplementary material The online version of this article (10.1007/s10549-019-05135-w) contains supplementary material, which is available to authorized users.

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Th1high in tumor microenvironment is an indicator of poor prognosis for patients with NSCLC

Cited by 22 publications

References 34 publications

An immunogenic NSCLC microenvironment is associated with favorable survival in lung adenocarcinoma

An immunogenic NSCLC microenvironment is associated with favorable survival in lung adenocarcinoma

Aberrant control of NF-κB in cancer permits transcriptional and phenotypic plasticity, to curtail dependence on host tissue: molecular mode

A high-risk luminal A dominant breast cancer subtype with increased mobility

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