Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer

Wang, Sisi; Liu, Wei; Ly, Dalam; Xu, Hao; Qu, Limei; Zhang, Li

doi:10.1038/s41423-018-0027-x

Cited by 395 publications

(297 citation statements)

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“…b ). A pervious study reported that B cells could be stimulated by tumor cells and then release growth factors to facilitate tumor growth . Here we examined whether lymphocytes cocultured with HNSCC cells could secrete more LT‐α.…”

Section: Resultsmentioning

confidence: 99%

“…A pervious study reported that B cells could be stimulated by tumor cells and then release growth factors to facilitate tumor growth. 27 Here we examined whether lymphocytes cocultured with HNSCC cells could secrete more LT-α. To this end, freshly isolated lymphocytes from the peripheral blood of healthy donors were cocultured with the human HNSCC cell line Cal27.…”

Section: Infiltrated Lymphocytes In Hnscc Secret Lymphotoxin-αmentioning

confidence: 99%

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Lymphotoxin‐α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3‐dependent manner

Yang

Wang

Xia

et al. 2019

Intl Journal of Cancer

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Tumor angiogenesis is critical for tumor progression as the new blood vessels supply nutrients and facilitate metastasis. Previous studies indicate tumor associated lymphocytes, including B cells and T cells, contribute to tumor angiogenesis and tumor progression. The present study aims to identify the function of Lymphotoxin‐α (LT‐α), which is secreted by the activated lymphocytes, in the tumor angiogenesis of head and neck squamous cell carcinoma (HNSCC). The coculture system between HNSCC cell line Cal27 and primary lymphocytes revealed that tumor cells promoted the LT‐α secretion in the cocultured lymphocytes. In vitro data further demonstrated that LT‐α promoted the proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) by enhancing the PFKFB3‐mediated glycolytic flux. Genetic and pharmacological inhibition of PFKFB3 suppressed the enhanced proliferation and migration of HUVECs. We further identified that LT‐α induced PFKFB3 expression was dependent on the TNFR/NF‐κB signaling pathway. In addition, we proved that PFKFB3 blockade decreased the density of CD31 positive blood vessels in HNSCC xenografts. Finally, the results from the human HNSCC tissue array revealed that the expression of LT‐α in HNSCC samples positively correlated with microvessel density, lymphocytes infiltration and endothelial PFKFB3 expression. In conclusion, infiltrated lymphocyte secreted LT‐α enhances the glycolysis of ECs in a PFKFB3‐dependent manner through the classical NF‐κB pathway and promotes the proliferation and migration of ECs, which may contribute to the aberrant angiogenesis in HNSCCs. Our study suggests that PFKFB3 blockade is a promising therapeutic approach for HNSCCs by targeting tumor angiogenesis.

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Section: Resultsmentioning

confidence: 99%

Section: Infiltrated Lymphocytes In Hnscc Secret Lymphotoxin-αmentioning

confidence: 99%

Lymphotoxin‐α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3‐dependent manner

Yang

Wang

Xia

et al. 2019

Intl Journal of Cancer

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“…These findings suggest that CLEC3B may play an important role in immune infiltration of SCC. The correlations between CLEC3B and immune markers of immune cells (selected by investigating some relevant papers [27][28][29][30][31]) were analyzed in the TIMER database to explore the relationship between CLEC3B and immune infiltrating cells of ADC and SCC (Table 6). In SCC, CLEC3B expression was positively correlated with majority of gene markers of different functional T cells (CD8+ T, Th1, Th2, etc.…”

Section: Clec3b Expression Is Associated With Immune Infiltration Inmentioning

confidence: 99%

CLEC3B as a potential diagnostic and prognostic biomarker in lung cancer and association with the immune microenvironment

et al. 2020

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Background: Lung cancer is the leading cause of cancer-related mortality globally. Discovering effective biomarkers for early diagnosis and prognosis is important to reduce the mortality rate and ensure efficient therapy for lung cancer patients. C-type lectin domain family 3 member B (CLEC3B) has been reported in various cancers, but its correlation with lung cancer remains elusive. Methods:The GEO, TCGA and Oncomine databases were analyzed to examine the expression of CLEC3B in lung cancer. The CLEC3B mRNA levels in 15 patient tissue samples were detected by real-time PCR and the CLEC3B protein levels in 34 patient tissue samples were detected by immunohistochemistry. A Chi-square test was performed to analyze the correlation of CLEC3B expression and clinicopathological factors. The diagnostic value of CLEC3B was revealed by receiver operating characteristic (ROC) curves. Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier plots were used to evaluate the prognostic value of CLEC3B in lung cancer. The TIMER database was used to evaluate the correlation of CLEC3B and immune infiltration. Gene set enrichment analysis revealed tumor-associated biological processes related to CLEC3B.Results: CLEC3B is significantly downregulated in lung cancer patients compared with nontumor controls according to database analysis and patient tissue sample detection (p < 0.001). Specifically, CLEC3B is significantly downregulated in stage IA lung cancer patients (p < 0.001) and has a high diagnostic accuracy (area under the receiver operating characteristic curve > 0.9). Moreover, low expression of CLEC3B is related to poor progression-free survival (HR = 0.60, 95% CI 0.49-0.74, p = 8.3e−07) and overall survival (HR = 0.66, 95% CI 0.58-0.75, p = 2.1e−10), indicating it as a risk factor for lung cancer. Multivariate analysis value showed that low expression of CLEC3B may be an independent risk factor for disease-free survival in lung cancer patients (HR = 0.655, 95% CI 0.430-0.996, Cox p = 0.048). In addition, we also investigated the potential role of CLEC3B in tumor-immune interactions and found that CLEC3B might be associated with the immune infiltration and immune activation of lung cancer, especially in squamous cell carcinoma.© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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“…Tumor-infiltrating immune cells play an important role in promoting or inhibiting tumor growth. As an integral part of the tumor microenvironment, tumor-infiltrating immune cells exist in all stages of cancer and play a vital role in shaping the development of tumors 54 . To study the effect of immune cell infiltration on the tumor microenvironment on the prognosis of LUAD patients, we used the TIMER to calculate the extent of infiltrations of CD4 + T cells, CD8 + T cells, B cells, neutrophils, macrophages, and dendritic cells and correlated the data with the expression of the identified crucial prognostic genes.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of lung adenocarcinoma

Luo

Cao

2020

Preprint

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Background: Lung adenocarcinoma (LUAD) is the most common primary lung cancer, and increasing evidence indicates the clinical importance of the microenvironment in LUAD. Tumor-infiltrating immune cells play an important role in promoting or inhibiting tumor growth. This study aimed to identify immune-related prognostic genes that were associated with the LUAD microenvironment. Methods:We used the "estimate" R package to calculate the immune/stromal scores of each sample of GSE72094 based on the ESTIMATE algorithm. Then we looked up relationships between patients' characteristics and immune/stromal scores. After that, we divided the samples into two groups: high and low scores, identified the common differentially expressed genes (DEGs), and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) on the common DEGs. After conducting the overall survival analysis of the common DEGs, prognostic genes were harvested. Then we constructed the protein-protein interaction network and performed the enrichment of GO and KEGG for the prognostic genes. Crucial prognostic genes were obtained after validating in two independent data sources (GSE68465 and TIMER). Finally, we investigated the immune correlates of the crucial prognostic genes based on the TIMER. Results:Immune scores did not vary with gender, age, smoking history, tumor stage, and EGFR status, but vary with the status of KRAS, STK11, and TP53. For the stromal scores, only the status of STK11 and TP53 mattered. Reduced immune score predicted poor prognosis of LUAD. 357 common DEGs were found, of which 108 were identified as prognostic genes after overall survival analysis. GO and KEGG analysis found that common DEGs and prognostic genes were both mainly involved in immune-related items. After validation in two independent data sources, 12 genes were validated to be crucial prognostic genes linked to prognosis. After investigated the TIMER, all 12 genes were correlated with the main immune cell types.Conclusion: 12 immune-related prognostic genes were discovered relating to the microenvironment in LUAD. These findings suggest that the composition of the tumor microenvironment affects the clinical outcomes of LUAD, and it may provide a basis for the development of novel prognostic biomarkers and immunotherapy for LUAD.

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Tumor-infiltrating B cells: their role and application in anti-tumor immunity in lung cancer

Cited by 395 publications

References 93 publications

Lymphotoxin‐α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3‐dependent manner

Lymphotoxin‐α promotes tumor angiogenesis in HNSCC by modulating glycolysis in a PFKFB3‐dependent manner

CLEC3B as a potential diagnostic and prognostic biomarker in lung cancer and association with the immune microenvironment

Comprehensive analysis of prognostic immune-related genes in the tumor microenvironment of lung adenocarcinoma

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