MHC-II Signature Correlates With Anti-Tumor Immunity and Predicts anti-PD-L1 Response of Bladder Cancer

Yi, Ruibin; Hong, Shuo; Zhang, Yueming; Lin, Anqi; Ying, Haoxuan; Zou, Weidong; Wang, Qiongyao; Wei, Ting; Cheng, Quan; Zhu, Wei; Luo, Peng; Zhang, Jian

doi:10.3389/fcell.2022.757137

Cited by 22 publications

(18 citation statements)

References 67 publications

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“…Previous studies have shown, in tissue samples of patients with advanced melanoma, that the degree of CD8 + T cell infiltration can adequately predict the efficacy of PD-1/PD-L1 monoclonal antibody treatment ( Tumeh et al, 2014 ). Antigen treatment and presentation are also very important components of the anti-tumor immune response ( Wang et al, 2019 ; Yi et al, 2022 ), with previous studies showing that antigen treatment and signature presentation are related to a better prognosis for patients undergoing immunotherapy ( Wang et al, 2019 ). In the process of antigen presentation, TAP-mediated peptides are transported into the endoplasmic reticulum cavity, where they combine with MHC-I complex, finally resulting in T cells which recognize new cell surface antigens ( Schumacher and Schreiber, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

TCR Coexpression Signature Predicts Immunotherapy Resistance in NSCLC

Wang

Liu²,

et al. 2022

Front. Pharmacol.

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Background: Lung cancer has the highest morbidity and mortality rate among types of malignant tumors, and as such, research into prolonging the survival time of patients is vital. The emergence of immune checkpoint inhibitors (ICIs) has greatly improved the survival of patients with non-small cell lung cancer (NSCLC), however, the lack of effective biomarkers to predict the prognosis of immunotherapy has made it difficult to maximize the benefits. T cell receptor (TCR) is one of the most important components for recognizing tumor cells, and with this study we aim to clarify the relationship between TCR coexpression and the prognosis of NSCLC patients receiving immunotherapy.Methods: Univariate COX regression, logistics regression, and KM survival analysis were used to evaluate the relationship between TCR coexpression and the prognosis of immunotherapy. Additionally, CIBERSORT, Gene Set Enrichment Analysis (GSEA), and single-sample GSEA (ssGSEA) algorithms were used to evaluate the tumor immune microenvironment (TIME) of NSCLC patients.Results: Univariate Cox regression analysis showed that the TCR coexpression signature can be used as a clinical prognostic indicator for NSCLC patients receiving immunotherapy (p = 0.0205). In addition, those in the NSCLC group with a high TCR coexpression signature had significantly improved progression-free survival (PFS) (p = 0.014). In the ICI treatment cohort (GSE35640). In addition, there was a high infiltration of CD8+T cells, activated memory CD4+T cells, and M1 macrophages in the TIME of those with a high TCR coexpression signature. The results of pathway enrichment analysis showed that patients with a high TCR coexpression signature had significantly activated signal pathways such as lymphocyte proliferation and activation, chemokine binding, and inflammatory cytokine production. Also, we found that patients with a high TCR coexpression signature had an elevated T cell inflammation gene expression profile (GEP).Conclusion: We show that the TCR coexpression signature may be useful as a new biomarker for the prognosis of NSCLC patients undergoing immunotherapy, with high signatures indicating better treatment response. Additionally, we found that patients with a high TCR coexpression signature had tumor immune microenvironments with beneficial anti-tumor characteristics.

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Section: Discussionmentioning

confidence: 99%

TCR Coexpression Signature Predicts Immunotherapy Resistance in NSCLC

Wang

Liu²,

et al. 2022

Front. Pharmacol.

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“…MHC-II expression by cancer cells has an important role in antitumor immunity. Accordingly, independent studies showed an association between tumor-expressed MHC-II, enhanced antitumor immunity, and more favorable prognosis [ 50 , 51 , 52 , 55 ]. Tumor-expressed MHC-II also correlated with response to anti-PD-1/anti-PD-L1 [ 49 , 56 ].…”

Section: Discussionmentioning

confidence: 99%

Integration of miRNA:mRNA Co-Expression Revealed Crucial Mechanisms Modulated in Immunogenic Cancer Cell Death

Lamberti

Montico

Ravo³

et al. 2022

Biomedicines

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Immunogenic cell death (ICD) in cancer represents a functionally unique therapeutic response that can induce tumor-targeting immune responses. ICD is characterized by the exposure and release of numerous damage-associated molecular patterns (DAMPs), which confer adjuvanticity to dying cancer cells. The spatiotemporally defined emission of DAMPs during ICD has been well described, whereas the epigenetic mechanisms that regulate ICD hallmarks have not yet been deeply elucidated. Here, we aimed to examine the involvement of miRNAs and their putative targets using well-established in vitro models of ICD. To this end, B cell lymphoma (Mino) and breast cancer (MDA-MB-231) cell lines were exposed to two different ICD inducers, the combination of retinoic acid (RA) and interferon-alpha (IFN-α) and doxorubicin, and to non ICD inducers such as gamma irradiation. Then, miRNA and mRNA profiles were studied by next generation sequencing. Co-expression analysis identified 16 miRNAs differentially modulated in cells undergoing ICD. Integrated miRNA-mRNA functional analysis revealed candidate miRNAs, mRNAs, and modulated pathways associated with Immune System Process (GO Term). Specifically, ICD induced a distinctive transcriptional signature hallmarked by regulation of antigen presentation, a crucial step for proper activation of immune system antitumor response. Interestingly, the major histocompatibility complex class I (MHC-I) pathway was upregulated whereas class II (MHC-II) was downregulated. Analysis of MHC-II associated transcripts and HLA-DR surface expression confirmed inhibition of this pathway by ICD on lymphoma cells. miR-4284 and miR-212-3p were the strongest miRNAs upregulated by ICD associated with this event and miR-212-3p overexpression was able to downregulate surface expression of HLA-DR. It is well known that MHC-II expression on tumor cells facilitates the recruitment of CD4+ T cells. However, the interaction between tumor MHC-II and inhibitory coreceptors on tumor-associated lymphocytes could provide an immunosuppressive signal that directly represses effector cytotoxic activity. In this context, MHC-II downregulation by ICD could enhance antitumor immunity. Overall, we found that the miRNA profile was significantly altered during ICD. Several miRNAs are predicted to be involved in the regulation of MHC-I and II pathways, whose implication in ICD is demonstrated herein for the first time, which could eventually modulate tumor recognition and attack by the immune system.

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“…Also, their independent prognostic effect is better than TMB in many solid tumors such as bladder cancer and mammary adenocarcinoma. (Yi, Hong et al 2022) Therefore, the new biomarkers ALKBH1 and TRMT10B that elevate CD4+T cells can be hopefully more sensitive clinical covariates to patients' prognosis. CD4 helper T cells can also induce DCs migrating to lymph nodes, enhancing the presentation of tumor antigens (Cohen, Giladi et al 2022).…”

Section: Discussionmentioning

confidence: 99%

m1A Regulator ALKBH1 and TRMT10B as Potential Prognostic Biomarkers and Related to Tumor Immune Microenvironment in Pancreatic Adenocarcinoma

Huang

et al. 2022

Preprint

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Background N1-methyladenosine (m1A) RNA methylation is crucial in the carcinogenesis and tumorous molecular pathogenesis. However, the detailed pathogenic mechanism of m1A regulators in pancreatic adenocarcinoma (PAAD) has not been comprehensively researched. Therefore, the purpose of this study was to investigate the role of m1A in PAAD prognosis and tumor microenvironment (TME).Methods The relationship between m1A regulators and the PAAD prognosis was analyzed with cBioportal database. RNA-seq transcriptome was obtained from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases for differential expression analysis. The role of m1A regulators in the PAAD TME was analyzed with TISIDB database and R software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed by The Database for Annotation, Visualization, and Integrated Discovery (DAVID).Results In PAAD, we discovered 10 m1A regulators correlated to poor prognosis and were all upregulated. While up-regulated ALKBH1 and TRMT10B were associated with a better prognosis in PAAD patients. Further research found that ALKBH1 and TRMT10B significantly upregulated the infiltrating level of immune cells, especially CD4+ T cells. Additionally, they also affected the expression of immunomodulators, including CD276, TMEM173, TNFSF9, etc. Finally, GO and KEGG enrichment analysis proved that ALKBH1 and TRMT10B influenced the PAAD development by regulating the RNA polymerase II.Conclusion Promoted expression of ALKBH1 and TRMT10B was significantly related with a better prognosis in PAAD, the possible mechanism of which might associate with the alternation of the TME. ALKBH1 and TRMT10B were potential prognosis biomarkers and possible immunotherapeutic targets for PAAD.

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MHC-II Signature Correlates With Anti-Tumor Immunity and Predicts anti-PD-L1 Response of Bladder Cancer

Cited by 22 publications

References 67 publications

TCR Coexpression Signature Predicts Immunotherapy Resistance in NSCLC

TCR Coexpression Signature Predicts Immunotherapy Resistance in NSCLC

Integration of miRNA:mRNA Co-Expression Revealed Crucial Mechanisms Modulated in Immunogenic Cancer Cell Death

m1A Regulator ALKBH1 and TRMT10B as Potential Prognostic Biomarkers and Related to Tumor Immune Microenvironment in Pancreatic Adenocarcinoma

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