Downregulation of TAP1 and TAP2 in early stage breast cancer

Henle, Andrea M.; Nassar, Aziza; Puglisi-Knutson, Danell; Youssef, Bahaaeldin; Knutson, Keith L.

doi:10.1371/journal.pone.0187323

Cited by 42 publications

(37 citation statements)

References 35 publications

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“…Endoplasmic reticulum without TAP1 and TAP2 induces the dysfunction of class I MHC molecules (60)(61)(62), thereby inhibiting the activity of CD8 + T cells. TAP was demonstrated have a prognostic protective effect in lung cancer, cervical cancer, breast cancer, and head and neck cancer (63)(64)(65)(66).…”

Section: Discussionmentioning

confidence: 97%

CD8+ T Cell Co-Expressed Genes Correlate With Clinical Phenotype and Microenvironments of Urothelial Cancer

et al. 2020

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PurposeTo identify immune-related co-expressed genes that promote CD8+ T cell infiltration in bladder cancer, and to explore the interactions among relevant genes in the tumor microenvironment.MethodWe obtained bladder cancer gene matrix and clinical information data from TCGA, GSE32894 and GSE48075. The “estimate” package was used to calculate tumor purity and immune score. The CIBERSORT algorithm was used to assess CD8+ T cell proportions. Weighted gene co-expression network analysis was used to identify the co-expression modules with CD8+ T cell proportions and bladder tumor purity. Subsequently, we performed correlation analysis among angiogenesis factors, angiogenesis inhibitors, immune inflammatory responses, and CD8+ T cell related genes in tumor microenvironment.ResultsA CD8+ T cell related co-expression network was identified. Eight co-expressed genes (PSMB8, PSMB9, PSMB10, PSME2, TAP1, IRF1, FBOX6, ETV7) were identified as CD8+ T cell-related genes that promoted infiltration of CD8+ T cells, and were enriched in the MHC class I tumor antigen presentation process. The proteins level encoded by these genes (PSMB10, PSMB9, PSMB8, TAP1, IRF1, and FBXO6) were lower in the high clinical grade patients, which suggested the clinical phenotype correlation both in mRNA and protein levels. These factors negatively correlated with angiogenesis factors and positively correlated with angiogenesis inhibitors. PD-1 and PD-L1 positively correlated with these genes which suggested PD-1 expression level positively correlated with the biological process composed by these co-expression genes. In the high expression group of these genes, inflammation and immune response were more intense, and the tumor purity was lower, suggesting that these genes were immune protective factors that improved the prognosis in patients with bladder cancer.ConclusionThese co-expressed genes promote high levels of infiltration of CD8+ T cells in an immunoproteasome process involved in MHC class I molecules. The mechanism might provide new pathways for treatment of patients who are insensitive to PD-1 immunotherapy due to low degrees of CD8+ T cell infiltration.

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Section: Discussionmentioning

confidence: 97%

CD8+ T Cell Co-Expressed Genes Correlate With Clinical Phenotype and Microenvironments of Urothelial Cancer

et al. 2020

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“…UBD, a member of the ubiquitin-like protein (UBL) family, is involved in various essential cellular development processes, including immune-mediated inflammation, apoptosis, cell cycle progression, and proliferation [ 29 , 30 ]. Transporter associated with antigen processing 1 (TAP1) is essential for peptide delivery from the cytosol to the lumen of the endoplasmic reticulum in the major histocompatibility complex (MHC) class I antigen-presenting pathway [ 31 ]. As described above, Guanylate-binding protein (GBP) 5 belongs to the GBP family, which is involved in important cellular processes, including signal transduction, translation, vesicle trafficking, and exocytosis [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Immune profiling reveals prognostic genes in high-grade serous ovarian cancer

Xia

Zhao

et al. 2020

Aging

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High-grade serous ovarian cancer (HGSOC) is a heterogeneous disease with diverse clinical outcomes, highlighting a need for prognostic biomarker identification. Here, we combined tumor microenvironment (TME) scores with HGSOC characteristics to identify immune-related prognostic genes through analysis of gene expression profiles and clinical patient data from The Cancer Genome Atlas and the International Cancer Genome Consortium public cohorts. We found that high TME scores (TMEscores) based on the fractions of immune cell types correlated with better overall survival. Furthermore, differential expression analysis revealed 329 differentially expressed genes between patients with high vs. low TMEscores. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed that these genes participated mainly in immune-related functions and, among them, 48 TME-related genes predicted overall survival in HGSOC. Seven of those genes were associated with prognosis in an independent HGSOC database. Finally, the two genes with the lowest p -values in the prognostic analysis (GBP1, ETV7) were verified through in vitro experiments. These findings reveal specific TME-related genes that could serve as effective prognostic biomarkers for HGSOC.

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“…Overexpression of the TAP1 protein has been suggested as an indicator of aggressiveness in breast cancers, which is thought to be due either to a lower capacity of more advanced tumors to downregulate TAP, or to a higher concentration of immune infiltrates in the microenvironment producing IFN-γ, which causes upregulation of the TAP subunits [ 18 ]. In colorectal cancer, decreased levels of TAP1 were seen in tumors with perineural invasion, making downregulation of TAP1 a prognostic factor for patients with stage I and II disease [ 19 ].…”

Section: Discussionmentioning

confidence: 99%

Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival

Attaran

Coates

et al. 2020

IJMS

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Oral cancers are surrounded by epithelium that histologically might seem normal, but genetically has aberrations. In patients with squamous cell carcinoma of the oral tongue (SCCOT), it is therefore important to study not only the tumor but also the clinically tumor-free contralateral tongue tissue that remains in the patient after treatment to map changes of prognostic and/or diagnostic value. The transporter associated with antigen processing (TAP) dimer is a key factor in the process of activating cytotoxic T cells. By downregulating the expression of TAP, tumor cells can escape cytotoxic T cell recognition. Biopsies from tumor and clinically tumor-free contralateral tongue tissue in 21 patients with SCCOT were analyzed together with tongue biopsies from 14 healthy individuals, which served as the control group. Dividing patients into TAP1-high and TAP1-low groups according to the median TAP1 level in tumor-free samples showed that patients with lower TAP1 mRNA levels in tumor-free samples had better overall (p = 0.003) and disease-free survival (p = 0.002). The results showing that TAP1 levels in tumor-free tongue tissue contralateral to the SCCOT correlate with survival is an important contribution to early diagnosis and follow up of SCCOT.

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Downregulation of TAP1 and TAP2 in early stage breast cancer

Cited by 42 publications

References 35 publications

CD8+ T Cell Co-Expressed Genes Correlate With Clinical Phenotype and Microenvironments of Urothelial Cancer

CD8+ T Cell Co-Expressed Genes Correlate With Clinical Phenotype and Microenvironments of Urothelial Cancer

Immune profiling reveals prognostic genes in high-grade serous ovarian cancer

Downregulation of TAP1 in Tumor-Free Tongue Contralateral to Squamous Cell Carcinoma of the Oral Tongue, an Indicator of Better Survival

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