Co-expression of cancer-testis antigens of MAGE-A6 and MAGE-A11 is associated with tumor aggressiveness in patients with bladder cancer

Mohsenzadegan, Monireh; Razmi, Mahdieh; Vafaei, Somayeh; Abolhasani, Maryam; Madjd, Zahra; Zanjani, Leili Saeednejad; Sharifi, Laleh

doi:10.1038/s41598-021-04510-2

Cited by 14 publications

(15 citation statements)

References 78 publications

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“…NY-ESO-1 and XAGE-1B are one of the CTAs, which are a large family of tumor-associated antigens only in germ cells of the testis and placenta ( 12 , 13 ), and in various malignant tumors, such as melanoma ( 14 ), squamous cell carcinoma ( 15 ), non-small cell lung cancer ( 16 ), gastric cancer ( 17 ), hepatocellular carcinoma ( 18 ), breast cancer ( 19 ), ovarian cancer ( 20 ), bladder cancer ( 21 ), prostate cancer ( 22 ), multiple myeloma ( 23 ), synovial sarcoma ( 24 ), and Ewing’s sarcoma ( 25 ). CTAs can be divided into two groups, those that are encoded on the X chromosome (CT-X antigens) and those that are not (non-X CT antigens) ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures

et al. 2023

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Cutaneous angiosarcoma (CAS) is a highly malignant tumor with few effective treatments. Although the indication for immune checkpoint inhibitors such as anti-PD-1 antibodies is expected to expand, there are many unknowns regarding the tumor immune microenvironment in CAS, which is generally considered an immunologically “cold” tumor. Our previous study demonstrated that tertiary lymphoid structures (TLSs) were associated with a favorable prognosis in CAS. However, we still don’t know what the difference is between cases of TLS-rich and TLS-poor. Furthermore, the number of TLSs can vary significantly between lesions in the same case, for example, between primary and recurrence. To analyze the changes in the tumor immune microenvironment in CAS in more detail, we performed comprehensive RNA sequencing using a Next-generation sequencer (NGS). Sixty-two samples from 31 cases of CAS treated at Nagoya City University were collected. NGS and gene set enrichment analysis (GSEA) were performed on 15 samples among them. Immunohistochemistry and prognostic analysis by Kaplan-Meier method were performed on all 62 samples. NGS results showed that NY-ESO-1 (CTAG1B) was significantly upregulated in the TLS-positive cases. Immune checkpoint molecules including programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) were upregulated in TLS-negative or TLS-low cases and seemed to associate with the suppression of TLS formation. In a comparison of primary and recurrent lesions, other cancer-testis antigens (CTAs) including XAGE-1B were significantly upregulated in recurrent lesions. The number of infiltrating CD8-positive cells and TLSs showed no significant trend between primary and recurrent lesions. However, the PD-L1 expression of tumor cells was significantly lower in recurrent than in primary lesions. Chemokines correlated with NY-ESO-1 expression were CCL21 and CXCL8, and only CCL21 correlated with the number of TLS. There was no chemokine associated with XAGE-1. NY-ESO-1 and XAGE-1 are detectable by immunohistochemistry. Although each cannot be a prognostic marker by itself, they can be a helpful marker in combination with the number of TLSs. CTAs play an essential role in forming the tumor immune microenvironment in CAS. These findings are evidence that CAS is an immunologically “hot” tumor and provides us with potential therapeutic targets and encourages the expansion of immunotherapy indications.

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Section: Discussionmentioning

confidence: 99%

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures

et al. 2023

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“…Although the mechanism responsible for the slight difference in effects between MSCderived exosomes and MSC's conditioned media is unclear, the study clari ed that exosomes act against tumor development by reducing the expression of MAGE6 and MAGE11 cell surface receptors. MAGE-A6 and MAGE11 are proto-oncogenes that affect various signaling pathways involved in tumor growth and progression (40,41). Previous studies have indicated that MAGEA6 positively regulates MSMO1 which may serve an oncogenic role in cells through this regulatory effect and promote the migration and invasion of esophageal cancer cells (40).…”

Section: Discussionmentioning

confidence: 99%

“…In particular, the melanoma-associated antigen-A (MAGE-A) family is the most important group of highly CTAs that is upregulated in different cancer types such as prostate cancer, breast cancer, lung cancer, and colorectal cancers (11,12), Increased cell motility and resistance to apoptosis are correlated with their expression (13). Numerous recent studies have shown that MAGE-A antigens are valuable prognostic markers and therapeutic targets for cancer immunotherapy (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

The effect of Mesenchymal stem cells- derived exosomes on the expression of MAGEA6 and MAGEA11 in a human colorectal carcinoma cell line

Azimi

Aghamajidi

Khosroshahi

et al. 2023

Preprint

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Background: Melanoma Antigen Gene (MAGE) proteins belong to a large, highly conserved family of proteins with a common homology domain. Most MAGE proteins are expressed exclusively in reproductive tissues, but they are aberrantly expressed in many types of cancer. In this study, we aimed to investigate the effects of adipose-derived mesenchymal stem cells secreted exosomes on the expression of MAGEA6 and MAGEA11 genes in the HCT-116 tumor cell line. Materials and Methods: Ad-MSCs were assessed for their surface antigenic profile using specific markers. TEM and western blot were used to evaluate the quality of the isolated exosomes, which were purified from the Ad-MSc supernatant. HCT-116 cells were co-cultured with MSC-conditioned medium (MSC-CM) and/or with 100 ug/ml of MSC-derived exosomes for 48h. Real-time PCR was carried out to determine the expression of MAGEA6 and MAGEA11 in HCT-116. Relative expression levels were calculated using the 2-ΔΔct method. Results: Our result showed that MAGEA11 mRNA expression levels were significantly reduced in exosome (EXO) and/or CM (MSC- conditioned medium) +EXO treated HCT116 while MAGEA6 mRNA expression levels were significantly reduced in CM+EXO treated HCT116 (P-value < 0.05). Conclusion: The current study showed that MSC-derived exosomes could inhibit the expression of two important molecules involved in tumor progression. Hence it seems MSCs-derived exosomes may hold a hopeful future as drug delivery vehicles that need further investigation.

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“…Interestingly, the most upregulated genes in EAC subtype 1 were from the melanoma antigen gene (MAGE) family ( Figure 6 A), which have potential value as targets of immunotherapies, since these proteins are also cancer/testis antigens [ 50 ]. MAGEs have been reported to promote tumor growth via a variety of pathways, resulting in more aggressive, metastatic tumors with higher risk of recurrence [ 51 ]. Further studies on MAGE function may facilitate the development of immunotherapy in EAC [ 52 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response

et al. 2022

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A low response rate limits the application of immune checkpoint inhibitors (ICIs) in the treatment of esophageal adenocarcinoma (EAC), which requires the precise characterization of heterogeneous tumor microenvironments. This study aimed to identify the molecular features and tumor microenvironment compositions of EAC to facilitate patient stratification and provide novel strategies to improve clinical outcomes. Here, we performed consensus molecular subtyping with nonnegative matrix factorization (NMF) using EAC data from the Cancer Genome Atlas (TCGA) and identified two distinct subtypes with significant prognostic differences and differences in tumor microenvironments. The findings were further validated in independent EAC cohorts and potential response to ICI therapy was estimated using Tumor Immune Dysfunction and Exclusion (TIDE) and SubMap methods. Our findings suggest that EAC patients of subtype 2 with low levels of cancer-associated fibroblasts, tumor associated macrophages (TAMs), and MDSCs in the tumor microenvironment may benefit from PD-1 blockade therapy, while patients of subtype 1 are more responsive to chemotherapy or combination therapy. These findings might improve our understanding of immunotherapy efficacy and be useful in the development of new strategies to better guide immunotherapy and targeted therapy in the treatment of EAC.

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Co-expression of cancer-testis antigens of MAGE-A6 and MAGE-A11 is associated with tumor aggressiveness in patients with bladder cancer

Cited by 14 publications

References 78 publications

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures

Tumor immune microenvironment of cutaneous angiosarcoma with cancer testis antigens and the formation of tertiary lymphoid structures

The effect of Mesenchymal stem cells- derived exosomes on the expression of MAGEA6 and MAGEA11 in a human colorectal carcinoma cell line

Identification of Immune Subtypes of Esophageal Adenocarcinoma to Predict Prognosis and Immunotherapy Response

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