Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence

Peng, Haitao; Xiao-yue, WU; Zhong, Ran; Yu, Tao; Liu, Jun; Wen, Yujie; Ao, Yiyuan; Chen, Jiana; Li, Yutian; He, Miao; Li, Caichen; Zheng, Hongbo; Chen, Yanhui; Pan, Zhenkui; He, Jianxing; Liang, Wenhua

doi:10.3389/fimmu.2021.750046

Cited by 34 publications

(35 citation statements)

References 51 publications

(25 reference statements)

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“…used multiplex immunofluorescence to demonstrate that patients with high levels of immune cell infiltration had the longest disease-free survival (DFS). Patients with low immune cell infiltration but rich in cancer stem cells and macrophages suffered worst prognosis ( 36 ). In breast cancer, it was reported that high levels of immune infiltration were associated with good clinical outcomes ( 37 ).…”

Section: Discussionmentioning

confidence: 99%

CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma

et al. 2022

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BackgroundThe tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD).MethodsThe gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein–protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues.ResultsWe identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan–Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis.ConclusionCSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies.

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Section: Discussionmentioning

confidence: 99%

CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma

et al. 2022

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“…Increased peripheral CD8 + CD28 + T cells correlated with favorable survival and better treatment response for patients with NSCLC [32][33][34]. Studies have indicated that high levels of tumor-infiltrated and peripheral Tregs were related to unfavorable prognosis in NSCLC compared with normal levels [35][36][37]. Thus, higher TMB, B cells, CD8 + T cells, and NK cells, among others, may be the reason that ICI was more effective in patients with GMS-low than in those with GMS-high.…”

Section: Discussionmentioning

confidence: 99%

“…MSI analysis could be an appropriate biomarker, while the low incidence of MSI-H in lung cancer might limit its clinical application in this population [38]. Emerging studies indicated that gene mutations including ARID1A, TP53, PBRM1, KEAP1, STK11, NOTCH, and JAK may have different effects for ICI treatment [32][33][34][35][36]. Nevertheless, a single gene mutation may not be adequate to transform the ICI treatment landscape and probably is not a sufficient comprehensive biomarker.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of a genomic mutation signature as a predictor for immunotherapy in NSCLC

Wang

et al. 2022

Bioscience Reports

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Currently, the benefits of immune checkpoint inhibitor (ICI) therapy prediction via emerging biomarkers have been identified, and the association between genomic mutation signatures and immunotherapy benefits has been widely recognized as well. However, the evidence about non-small cell lung cancer (NSCLC) remains limited. We analyzed 310 immunotherapy patients with NSCLC from the Memorial Sloan Kettering Cancer Center (MSKCC) cohort. Lasso Cox regression was used to construct a genomic mutation signature (GMS), and the prognostic value of GMS could be able to verify in the Rizvi cohort (N = 240) and Hellmann cohort (N = 75). We further conducted immunotherapy-related characteristics analysis in TCGA cohort (N = 1052). A total of seven genes (ZFHX3, NTRK3, EPHA7, MGA, STK11, EPHA5, TP53) were identified for GMS model construction. Compared with GMS-high patients, patients with GMS-low had longer overall survival (P < 0.001) in the MSKCC cohort and progression-free survival (P < 0.001) in the validation cohort. Multivariate Cox analysis revealed that GMS was an independent predictive factor for NSCLC patients in both the MSKCC and validation cohort. Meanwhile, we found that GMS-low patients reflected enhanced anti-tumor immunity in TCGA cohort. The results indicated that GMS had not only potential predictive value for the benefit of immunotherapy, but also may serve as a potential biomarker to guide clinical ICI treatment decisions for NSCLC.

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“…An immunohistochemistry-based study of NSCLC also found that most patients are clustered into a subtype classified as ‘immune activated’, characterized by high CD4+ T cells, CD8+ T cells and CD20+ B cells, which subsequently associated with longer disease-free survival in treatment naïve early stage resected NSCLC patients. However, they also observed 2 other clustered subsets of NSCLC patients that had increased expression of CD133 and FoxP3, and these were associated with shorter disease-free survival ( 85 ).…”

Section: Site Specific Clinical Outcomes and The Tumor Microenvironmentmentioning

confidence: 99%

The effect of organ-specific tumor microenvironments on response patterns to immunotherapy

Conway

Braden²,

Wilmott³

et al. 2022

Front. Immunol.

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Immunotherapy, particularly immune checkpoint inhibitors, have become widely used in various settings across many different cancer types in recent years. Whilst patients are often treated on the basis of the primary cancer type and clinical stage, recent studies have highlighted disparity in response to immune checkpoint inhibitors at different sites of metastasis, and their impact on overall response and survival. Studies exploring the tumor immune microenvironment at different organ sites have provided insights into the immune-related mechanisms behind organ-specific patterns of response to immunotherapy. In this review, we aimed to highlight the key learnings from clinical studies across various cancers including melanoma, lung cancer, renal cell carcinoma, colorectal cancer, breast cancer and others, assessing the association of site of metastasis and response to immune checkpoint inhibitors. We also summarize the key clinical and pre-clinical findings from studies exploring the immune microenvironment of specific sites of metastasis. Ultimately, further characterization of the tumor immune microenvironment at different metastatic sites, and understanding the biological drivers of these differences, may identify organ-specific mechanisms of resistance, which will lead to more personalized treatment approaches for patients with innate or acquired resistance to immunotherapy.

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Profiling Tumor Immune Microenvironment of Non-Small Cell Lung Cancer Using Multiplex Immunofluorescence

Cited by 34 publications

References 51 publications

CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma

CSF2RB Is a Unique Biomarker and Correlated With Immune Infiltrates in Lung Adenocarcinoma

Identification and validation of a genomic mutation signature as a predictor for immunotherapy in NSCLC

The effect of organ-specific tumor microenvironments on response patterns to immunotherapy

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