Targeting Versican as a Potential Immunotherapeutic Strategy in the Treatment of Cancer

Hirani, Priyanka; Gauthier, Valentine; Allen, Carys E.; Wight, Thomas N.; Pearce, Oliver M.T.

doi:10.3389/fonc.2021.712807

Cited by 20 publications

(11 citation statements)

References 110 publications

(152 reference statements)

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“…Both ITGB4 and VCAN are considered to correlate with ECM and promote tumor invasion and metastasis of breast cancer with elevated expression (38,40). Besides, VCAN also correlated strongly with immune suppression and may be responsible for immunotherapy failure (41), which is in line with the suppressed immune response of ACC in our data. DPT (dermatopontin) is a tyrosine-rich ECM protein, which principally takes a significant role in focal adhesion, matrix remodeling, and metastasis of cancer cells (42).…”

Section: Discussionsupporting

confidence: 89%

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer

et al. 2022

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BackgroundAdenoid cystic carcinoma (ACC) is a rare type of triple-negative breast cancer that has an indolent clinical behavior. Given the substantial overlapping morphological, immunohistochemical, and molecular features with other basal-like triple-negative breast cancer (BL-TNBC), accurate diagnosis of ACC is crucial for effective clinical treatment. The integrative analysis of the proteome and clinicopathological characteristics may help to distinguish these two neoplasms and provide a deep understanding on biological behaviors and potential target therapy of ACC.MethodsWe applied mass spectrometry-based quantitative proteomics to analyze the protein expression in paired tumor and adjacent normal breast tissue of five ACC and five BL-TNBC. Bioinformatic analyses and the clinicopathological characteristics, including histological features, immunohistochemistry, and FISH results, were also collected to get comprehensive information.ResultsA total of 307 differentially expressed proteins (DEPs) were identified between ACC and BL-TNBC. Clustering analysis of DEPs clearly separated ACC from BL-TNBC. GSEA found downregulation of the immune response of ACC compared with BL-TNBC, which is consistent with the negative PD-L1 expression of ACC. Vesicle-mediated transport was also inhibited, while ECM organization was enriched in ACC. The top upregulated proteins in DEPs were ITGB4, VCAN, and DPT. Moreover, in comparison with normal breast tissue, ACC showed elevated ribosome biogenesis and RNA splicing activity.ConclusionThis study provides evidence that ACC presents a substantially different proteomic profile compared with BL-TNBC and promotes our understanding on the molecular mechanisms and biological processes of ACC, which might be useful for differential diagnosis and anticancer strategy.

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Section: Discussionsupporting

confidence: 89%

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer

et al. 2022

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“…Surprisingly, our study demonstrates a correlation between the infiltration of CD8+ T cells and favorable prognosis in DLBCL. Here, we propose a hypothesis that in our study, the observed high expression of VCAN might create a suppressive environment for PD-1+ CD8+ T cells [21,38]. Intriguingly, our study revealed a statistically significant correlation between VCAN expression, C1QB expression and CD8+ T cell infiltration.…”

Section: Discussionsupporting

confidence: 63%

Tumor Purity-Related Genes for Predicting the Prognosis and Drug Sensitivity of DLBCL Patients

Ye,

Huang,

et al. 2023

Preprint

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BackgroundDiffuse large B-cell lymphoma (DLBCL) is the predominant type of malignant B-cell lymphoma. Although various treatments have been developed, the limited efficacy calls for more and further exploration of its characteristics.MethodsDatasets from Gene Expression Omnibus (GEO) database were used for identifying the tumor purity of DLBCL. Survival analysis was employed for analyzing the prognosis of DLBCL patients. Immunohistochemistry was conducted to detect the important factor that influenced the prognosis. Drug sensitive prediction was performed to evaluate the value of the constructed model.ResultsVCAN, CD3G and C1QB were identified as three key genes that impacted the outcome of DLBCL patients both in GEO datasets and samples from our center. Among them, VCAN and CD3G+ T cells were correlated with favorable prognosis, and C1QB was correlated with worse prognosis. The ratio of CD68+ macrophages and CD8+ T cells was associated with better prognosis. In addition, CD3G+ T cells ratio was significantly correlated with CD68+ macrophages, CD4+ T cells and CD8+ T cells ratio, indicating it could play an important role in the anti-tumor immunity in DLBCL. The riskScore model constructed based on the RNASeq data of VCAN, C1QB and CD3G work well in predicting the prognosis and drug sensitivity.ConclusionVCAN, CD3G and C1QB were three key genes that influenced the tumor purity of DLBCL, and could also exert certain impact on drug sensitivity and prognosis of DLBCL patients.

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“…In our previous work, we identified a specific tumor ECM signature that associated with disease progression and immunosuppression, identified in high-grade serous ovarian cancer (HGSOC) 1 , and shared by 12 other solid carcinomas, including those with limited treatment options such as pancreatic, lung, and esophageal cancers. This ECM signature associated with immunosuppressive cell phenotypes, but did not positively correlate with cytotoxic immune cell phenotypes, and negatively correlated with CD8 T cells 9 . Building on these studies, we applied computational algorithms CIBERSORTx and xCell to these previously gathered datasets 1 to further look at how specific ECM molecules associate with immune cell infiltrate.…”

Section: Introductionmentioning

confidence: 82%

Extracellular matrix educates a tumor macrophage phenotype found in ovarian cancer metastasis

Puttock

Tyler

Manni

et al. 2022

Preprint

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Recent studies have shown the tumor extracellular matrix (ECM) associates with immunosuppression, and that targeting the ECM can improve immune infiltration and immunotherapy response. A question that remains is whether the ECM is directly educating the immune phenotypes seen in cancer. We identified a tumor-associated macrophage (TAM) population correlated with poor prognosis, interruption of the cancer immunity cycle, and tumor ECM composition. To investigate whether ECM was capable of generating the TAM phenotype seen, we developed a decellularized tissue model that retains the native ECM architecture and composition. Macrophages cultured on decellularized ovarian metastasis shared transcriptional profiles with the TAMs found in human tissues. ECM educated macrophages have a tissue remodeling and immunoregulatory phenotype, inducing altered T cell function. We conclude that the tumor ECM is directly educating this macrophage population found in cancer tissues. Therefore, current and emerging cancer therapies that target the tumor ECM may be tailored to improve macrophage phenotype and their downstream regulation of immunity.

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Targeting Versican as a Potential Immunotherapeutic Strategy in the Treatment of Cancer

Cited by 20 publications

References 110 publications

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer

Comparative proteomic and clinicopathological analysis of breast adenoid cystic carcinoma and basal-like triple-negative breast cancer

Tumor Purity-Related Genes for Predicting the Prognosis and Drug Sensitivity of DLBCL Patients

Extracellular matrix educates a tumor macrophage phenotype found in ovarian cancer metastasis

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