111P A study on the relationship between tumor fusion burden (TFB) and tumor immune microenvironment

Abstract Background: The relationship between the pseudogene and tumor immune microenvironment in cutaneous melanoma is unclear. In this study, we analyzed the role of the pseudogene HLA-DRB6 and its effect on the tumor immune microenvironment in skin cutaneous melanoma (SKCM) using bioinformatics tools. Method: The GEPIA database was used to analyze the expression of HLA-DRB6 and CXCL10 mRNA in tumor tissues. The TIMER database was used to analyze the relationship between mRNA levels and the infiltration of immune cells. The enrichment of HLA-DRB6 and CXCL10 in melanoma tissues was analyzed by single cell portal. The binding sites of HLA-DRB6 with its target genes was predicted via starBase database. The gene expression profiling and clinical data from GEO database (GSE94873) was used to verify the potential of CXCL10 as a biomarker. Result: The expression of HLA-DRB6 in SKCM tumor is higher than in normal tissues, and patients with high HLA-DRB6 expression had a better prognosis (P<0.05). Furthermore, HLA-DRB6 is positively correlated with the infiltration of immune cells such as B cells, CD4+ T, and CD8+ T lymphocytes, and the expression of immune checkpoint molecules such as PD-1, PD-L1, and CTLA-4. Single cell transcriptome sequencing data showed that HLA-DRB6 is mainly enriched in macrophages and had the highest correlation with CXCL10 than other chemokines (cor=0.66, P<0.0001). In addition, we found that CXCL10 can be used as a potential biomarker for predicting responsiveness and survival rate in SKCM patients who treated with Tremelimumab (a human anti-CTLA-4 antibody). Conclusion: In the microenvironment of SKCM, HLA-DRB6 is mainly enriched in macrophages and regulates the expression of CXCL10 through the ceRNA mechanism. Furthermore, the CXCL10 in peripheral blood can be used as a biomarker to predict the responsiveness and the prognosis for patients treated with tremelimumab.

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m6A-Related lncRNAs Affect Tumor Immune Microenvironment And Prognosis In Acute Myeloid Leukemia

10.21203/rs.3.rs-897609/v1 ◽

2021 ◽

Author(s):

Fangmin Zhong ◽

Fangyi Yao ◽

Ying Cheng ◽

Jing Liu ◽

Nan Zhang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Cox Regression ◽

Risk Scores ◽

In Vitro Assays ◽

Immune Microenvironment ◽

Cox Regression Analysis ◽

Tumor Immune Microenvironment ◽

The Relationship ◽

Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a complex hematologic malignancy. Survival rate of AML patients is low. N6-methyladenosine (m6A) and long-chain non-coding RNAs (lncRNAs) play important roles in AML tumorigenesis and progression. However, the relationship between lncRNAs and biological characteristics of AML, as well as how lncRNAs influence the prognosis of AML patients, remain unclear. In this study, we identified m6A-related lncRNAs, and analyzed their roles and prognostic values in AML. m6A-related lncRNAs associated with patient prognosis were screened using univariate Cox regression analysis, followed by systematic analysis of the relationship between these genes and AML clinicopathologic and biologic characteristics. Furthermore, we examined the characteristics of tumor immune microenvironment (TIME) using different IncRNA clustering models. Using LASSO regression, we identified the risk signals related to prognosis of AML patients. We then constructed and verified a risk model based on m6A-related lncRNAs for independent prediction of overall survival in AML patients. Our results indicate that risk scores, calculated based on risk-related signaling, were related to the clinicopathologic characteristics of AML and level of immune infiltration. Finally, we examined the expression level of TRAF3IP2-AS1 in patient samples through real-time polymerase chain reaction analysis and in GEO datasets, and we identified SRSF10 as a regulator of TRAF3IP2-AS1 through in vitro assays. Our study shows that m6A-related lncRNAs, evaluated using the risk prediction model, can potentially be used to predict prognosis and design immunotherapy in AML patients.

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The Role of the Tumor Microenvironment and Treatment Strategies in Colorectal Cancer

Frontiers in Immunology ◽

10.3389/fimmu.2021.792691 ◽

2021 ◽

Vol 12 ◽

Author(s):

Yaping Chen ◽

Xiao Zheng ◽

Changping Wu

Keyword(s):

Colorectal Cancer ◽

Checkpoint Inhibitors ◽

Treatment Strategies ◽

Research Progress ◽

Immune Microenvironment ◽

Appropriate Treatment ◽

Tumor Immune Microenvironment ◽

The Relationship ◽

Selection Of

Colorectal cancer (CRC) has the second highest mortality rate among all cancers worldwide. Surgery, chemotherapy, radiotherapy, molecular targeting and other treatment methods have significantly prolonged the survival of patients with CRC. Recently, the emergence of tumor immunotherapy represented by immune checkpoint inhibitors (ICIs) has brought new immunotherapy options for the treatment of advanced CRC. As the efficacy of ICIs is closely related to the tumor immune microenvironment (TME), it is necessary to clarify the relationship between the immune microenvironment of CRC and the efficacy of immunotherapy to ensure that the appropriate drugs are selected. We herein review the latest research progress in the immune microenvironment and strategies related to immunotherapy for CRC. We hope that this review helps in the selection of appropriate treatment strategies for CRC patients.

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Progress in the Understanding of the Immune Microenvironment and Immunotherapy in Malignant Pleural Mesothelioma

Current Drug Targets ◽

10.2174/1389450121666200719011234 ◽

2020 ◽

Vol 21 (15) ◽

pp. 1606-1612 ◽

Cited By ~ 1

Author(s):

Lei Cheng ◽

Na Li ◽

Xiao-ling Xu ◽

Wei-Min Mao

Keyword(s):

Tumor Microenvironment ◽

Malignant Pleural Mesothelioma ◽

Asbestos Exposure ◽

Extrapleural Pneumonectomy ◽

Pleural Mesothelioma ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment ◽

Mechanism Of Carcinogenesis ◽

Cycle Regulation ◽

The Relationship

Malignant pleural mesothelioma (MPM) is a remarkably aggressive thoracic malignancy with a limited survival of only 5-12 months. However, MPM still remains unresponsive to conventional standards of treatment, including pleurectomy and decortication, extrapleural pneumonectomy for resectable disease with or without chemotherapy, and/or radiation therapy. The mechanism of carcinogenesis has not been fully elucidated, although approximately 80% of cases can still be linked to asbestos exposure. The tumor immune microenvironment (TME) has been proven to play an important role in MPM pathogenesis and treatment outcomes. Several molecular pathways have been implicated in the MPM tumor microenvironment, such as angiogenesis, apoptosis, cell cycle regulation, and stromal processes. Immunotherapy has already shown promising results in other thoracic solid tumors, such as non-small-cell lung cancer (NSCLC). However, immunotherapy has shown less convincing results in MPM than in melanoma and NSCLC. A multicenter, randomized trial (DETERMINE) proved that immune checkpoint inhibition using tremelimumab, an anti-cytotoxic T lymphocyteassociated protein 4 (CTLA-4) antibody, failed to improve median overall survival. Therefore, it is important to explore the relationship between the characteristics of the tumor microenvironment and immunotherapy. Here, we review the heterogeneity of the TME and the progress in the understanding of the immune microenvironment and immunotherapy in MPM to explore the mechanisms of resistance to immunotherapy.

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Analysis of N6-Methyladenosine Modification Patterns and Tumor Immune Microenvironment in Pancreatic Adenocarcinoma

Frontiers in Genetics ◽

10.3389/fgene.2021.752025 ◽

2022 ◽

Vol 12 ◽

Author(s):

Yong Liu ◽

Guangbing Li ◽

Yang Yang ◽

Ziwen Lu ◽

Tao Wang ◽

...

Keyword(s):

Pancreatic Adenocarcinoma ◽

Immune Cell ◽

Gene Clusters ◽

Rare Cancer ◽

Prognostic Role ◽

Immune Microenvironment ◽

Holistic Understanding ◽

Tumor Immune Microenvironment ◽

Potential Indicator ◽

The Relationship

Background: Pancreatic adenocarcinoma (PAAD) is a rare cancer with a poor prognosis. N6-methyladenosine (m6A) is the most common mRNA modification. However, little is known about the relationship between m6A modification and the tumor immune microenvironment (TIME) in PAAD.Methods: Based on 22 m6A regulators, m6A modification patterns of PAAD samples extracted from public databases were systematically evaluated and correlated with the tumor immune and prognosis characteristics. An integrated model called the “m6Ascore” was constructed, and its prognostic role was evaluated.Results: Three different m6Aclusters and gene clusters were successively identified; these clusters were characterized by differences in prognosis, immune cell infiltration, and pathway signatures. The m6Ascore was constructed to quantify the m6A modifications of individual patients. Subsequent analysis revealed that m6Ascore was an independent prognostic factor of PAAD and could be a potential indicator to predict the response to immunotherapy.Conclusion: This study comprehensively evaluated the features of m6A modification patterns in PAAD. m6A modification patterns play a non-negligible role in the TIME of PAAD. m6Ascore provides a more holistic understanding of m6A modification in PAAD, and will help clinicians predict the prognosis and response to immunotherapy.

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N6-Methyladenosine RNA Modification in the Tumor Immune Microenvironment: Novel Implications for Immunotherapy

Frontiers in Immunology ◽

10.3389/fimmu.2021.773570 ◽

2021 ◽

Vol 12 ◽

Author(s):

Liting Guo ◽

Hui Yang ◽

Chenfei Zhou ◽

Yan Shi ◽

Lei Huang ◽

...

Keyword(s):

Immune Cells ◽

Suppressor Cells ◽

Detection Methods ◽

Eukaryotic Cells ◽

Rna Modification ◽

Myeloid Derived Suppressor Cells ◽

Immune Microenvironment ◽

Cancer Occurrence ◽

Tumor Immune Microenvironment ◽

The Relationship

N6-methyladenosine (m6A) methylation is one of the most common modifications of RNA in eukaryotic cells, and is mainly regulated by m6A methyltransferases (writers), m6A demethylases (erasers), and m6A binding proteins (readers). Recently, accumulating evidence has shown that m6A methylation plays crucial roles in the regulation of the tumor immune microenvironment, greatly impacting the initiation, progression, and metastasis processes of various cancers. In this review we first briefly summarizes the m6A-related concepts and detection methods, and then describes in detail the associations of m6A methylation modification with various tumor immune components especially immune cells (e.g., regulatory T cells, dendritic cells, macrophages, and myeloid-derived suppressor cells) in a variety of cancers. We discuss the relationship between m6A methylation and cancer occurrence and development with the involvement of tumor immunity highlighted, suggesting novel markers and potential targets for molecular pathological diagnosis and immunotherapy of various cancers.

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NIR-active Nanoterminator with Mature Dendritic Cell Acitivities for Immuno-Priming Mild Photothermal Cancer Therapy

10.26434/chemrxiv.12546698 ◽

2020 ◽

Author(s):

zhihong sun ◽

Guanjun Deng ◽

Xinghua Peng ◽

Xiuli Xu ◽

Lanlan Liu ◽

...

Keyword(s):

Dendritic Cell ◽

Photothermal Therapy ◽

Whole Body ◽

Mature Dendritic Cell ◽

Immune Microenvironment ◽

Highly Efficient ◽

Tumor Immune Microenvironment ◽

Shock Proteins ◽

Mild Temperature ◽

Broad Interest

Recently, photothermal-immuno synergistic therapy under mild temperature (~ 45 °C) has got broad interest in cancer treatment. Inhibition the intratumorally HSPs production is the key to accomplish highly efficient and mild photothermal therapy. In this work, we developed biomimetic nanoterminators with mature DCs functions by coating the mature dendritic cell membrane on photothermal nanoagents. As-prepared nanoterminators could automatically locate on T cell in the complex tumor-immune microenvironment and promote the T cells proliferation, activation and cytokine secretion, which could not only inhibit the expression of heat shock proteins to cooperate on highly efficient mild photothermal therapy (~42°C), but also promote tumor apoptosis during the treatment. More importantly, this nanoterminator could serve as vaccine to trigger anti-tumor immune response of the whole body, which would be promising to long-life tumor inhibition and termination.

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