A Combination of Positive Tumor HLA-I and Negative PD-L1 Expression Provides an Immune Rejection Mechanism in Bladder Cancer

Flores-Martín, José Francisco; Perea, F.; Ruíz, Manuela Expósito; Carretero, Francisco Javier; Rodrı́guez, Teresa; Villamediana, Marina; Ruiz‐Cabello, Francisco; Garrido, Federico; Cózar-Olmo, J.M.; Aptsiauri, Natalia

doi:10.1245/s10434-019-07371-2

Cited by 17 publications

(10 citation statements)

References 33 publications

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“…Therefore, the problem of AML with unfavorable-risk cytogenetics deserves special attention. The GSEA of our study showed that DEGs mainly enriched in immune response (BP) regulated the occurrence and development of AML and in uence the prognosis of AML, which was consistent with the contributes of immune response to tumor progression and drug resistance in various cancers [22,23], including lung cancer [24], breast cancer [25] and bladder cancer [26]. We also found that IGHM genes were primarily enriched in the B cell mediated immunity and the B-cell receptor signaling pathway, these results indicate that the development and prognosis of AML may be related to these biological processes.…”

Section: Discussionsupporting

confidence: 82%

Analysis of the Differential Expression and Prognostic Relationship of DEGs in AML based on TCGA Database

Zhang

et al. 2020

Preprint

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Background: Acute myeloid leukemia (AML) is a common and lethal hematological malignant hyperplastic disease originating from hematopoietic stem cells. The purpose of this study is to obtain the key AML survival-related differentially expressed gene. Methods: RNA sequencing (RNA-Seq) data and clinical information of patients were downloaded from the TCGA-LAML database. We focused the intersectional genes of survival-related DEGs, cytogenetics risk related-DEGs, and the top 10 pathways of both up- and down-regulated of Normalization Enrichment Score (NES). Multivariate Cox regression analyses were performed to analyze the independent factors for AML. The Kaplan–Meier and Nomogram analyses were plotted to predict and compare survival of AML patients. The validation of DEGs were performed by a clinical follow-up investigation.Results: 151 RNA-Seq samples for 60,488 genes and 200 clinical samples were selected from the TCGA-database. After filtering with the conditions about survival-related DEGs, cytogenetics-risk associated, and predicted in top 10 pathways, IGHM was the only remaining gene. Cox analysis showed that IGHM expression and age displayed were intendent factors to the patients’ survival (P<0.05). Higher IGHM expression was identified in poor survival group (P<0.05), with 68%, 43%, and 30% in 1, 3, and 5-year survival investigation. GSEA analysis revealed that IGHM were mainly enriched in the immune response. In Chinese population, IGHM displayed its significance not in the childhood AML patients but in adult ones. Conclusion: High expression of IHGM gene is an independent risky factor for the survival of patients with AML, which can be an important molecular marker for AML prognosis.

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Section: Discussionsupporting

confidence: 82%

Analysis of the Differential Expression and Prognostic Relationship of DEGs in AML based on TCGA Database

Zhang

et al. 2020

Preprint

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“…A simultaneous analysis of tumor HLA-I and PD-L1 expression, together with the evaluation of the density and patterns of TILs, provide an important predictive marker for lung cancer progression and response to ICI [ 2 , 3 , 14 , 15 , 16 , 17 ]. We previously obtained similar results in bladder cancer [ 18 ] and here we further analyze the interaction of tumor cells with the stromal elements, including cancer associated fibroblasts, in the context of tumor immune infiltration and tumor HLA-I and PD-L1 expression.…”

Section: Introductionmentioning

confidence: 59%

Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes

Gil-Julio

Perea

Rodríguez-Nicolás

et al. 2021

IJMS

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Cancer eradication and clinical outcome of immunotherapy depend on tumor cell immunogenicity, including HLA class I (HLA-I) and PD-L1 expression on malignant cells, and on the characteristics of the tumor microenvironment, such as tumor immune infiltration and stromal reaction. Loss of tumor HLA-I is a common mechanism of immune escape from cytotoxic T lymphocytes and is linked to cancer progression and resistance to immunotherapy with the inhibitors of PD-L1/PD-1 signaling. Here we observed that HLA-I loss in bladder tumors is associated with T cell exclusion and tumor encapsulation with stromal elements rich in FAP-positive cells. In addition, PD-L1 upregulation in HLA-I negative tumors demonstrated a correlation with high tumor grade and worse overall- and cancer-specific survival of the patients. These changes define common immuno-morphological signatures compatible with cancer immune escape and acquired resistance to therapeutic interventions across different types of malignancy. They also may contribute to the search of new targets for cancer treatment, such as FAP-expressing cancer-associated fibroblasts, in refractory bladder tumors.

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“…Further classification of cases revealed 361 common DEGs between high vs low immune/stromal score patients. GO analysis of these DEGs revealed significant enrichment in immune-related processes known to contribute to disease progression and drug resistance in several tumors [34, 35], including lung cancer [36], breast cancer [37] and bladder cancer [38]. Accordingly, KEGG analysis suggested the involvement of DEGs in several signaling pathways including ‘chemokine signaling pathway’ [39] and ‘intestinal immune network for IgA production’ [40], which may influence TME dynamics and development of AML.…”

Section: Discussionmentioning

confidence: 99%

Identification of prognostic genes in the acute myeloid leukemia microenvironment

Huang

Zhang

Fan

et al. 2019

Aging

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The tumor microenvironment (TME) has a strong influence on the progression, therapeutic response, and clinical outcome of acute myeloid leukemia (AML), one of the most common hematopoietic malignancies in adults. In this study, we identified TME-related genes associated with AML prognosis. Gene expression profiles from AML patients were downloaded from TCGA database, and immune and stromal scores were calculated using the ESTIMATE algorithm. Immune scores were correlated with clinical features such as FAB subtypes and patient’s age. After categorizing AML cases into high and low score groups, an association between several differentially expressed genes (DEGs) and overall survival was identified. Functional enrichment analysis of the DEGs showed that they were primarily enriched in the immune response, inflammatory response, and cytokine activity, and were involved in signaling processes related to hematopoietic cell lineage, B cell receptor, and chemokine pathways. Two significant modules, dominated respectively by CCR5 and ITGAM nodes, were identified from the PPI network, and 20 hub genes were extracted. A total of 112 DEGs correlated with poor overall survival of AML patients, and 11 of those genes were validated in a separate TARGET-AML cohort. By identifying TME-associated genes, our findings may lead to improved prognoses and therapies for AML.

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A Combination of Positive Tumor HLA-I and Negative PD-L1 Expression Provides an Immune Rejection Mechanism in Bladder Cancer

Cited by 17 publications

References 33 publications

Analysis of the Differential Expression and Prognostic Relationship of DEGs in AML based on TCGA Database

Analysis of the Differential Expression and Prognostic Relationship of DEGs in AML based on TCGA Database

Tumor Escape Phenotype in Bladder Cancer Is Associated with Loss of HLA Class I Expression, T-Cell Exclusion and Stromal Changes

Identification of prognostic genes in the acute myeloid leukemia microenvironment

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