Correction to: Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data

Finotello, Francesca; Mayer, Clemens; Plattner, Christina; Laschober, Gerhard; Rieder, Dietmar; Hackl, Hubert; Krogsdam, Anne; Loncová, Zuzana; Posch, Wilfried; Wilflingseder, Doris; Sopper, Sieghart; Ijsselsteijn, Marieke E.; Brouwer, Thomas P.; Johnson, Douglas B.; Xu, Yaomin; Wang, Yu; Sanders, Melinda E.; Estrada, Mónica Valéria; Ericsson-Gonzalez, Paula I.; Charoentong, Pornpimol; Balko, Justin M.; Miranda, Noel F C C de; Trajanoski, Zlatko

doi:10.1186/s13073-019-0655-5

Cited by 56 publications

(35 citation statements)

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“…To evaluate immune infiltration and landscape of tumor immune microenvironment, whole transcriptomic expression data were uploaded in TIMER2.0 [ 35 ] ( http://timer.comp-genomics.org/ ). Six immune deconvolution algorithms: TIMER (TMR) [ 36 ], CIBERSORT (CBS & CBS-ABS) [ 37 ], quanTIseq (QTS) [ 38 ], xCell (XCL) [ 39 ], MCP-counter (MCP) [ 40 ] and EPIC (EPC) [ 41 ] were used to estimate the infiltration condition of various kinds of immune cells. Landscape heatmaps in both GSE77509 and TCGA cohort were drawn to uncover the composition of TIICs of all the samples in six algorithms.…”

Section: Methodsmentioning

confidence: 99%

Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

Zhang

et al. 2021

Cancer Cell Int

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Background Cumulating evidence reveals the key role of aberrant lipogenesis and immunogenomic features in hepatocellular carcinoma (HCC). However, there are still obstacles in our understanding of the complicated interaction between metabolic reprogramming and tumor immune microenvironment. Methods We compared metabolomic, transcriptomic and immunogenomic characteristics of portal vein tumor thrombosis (PVTT) and primary tumor to seek valuable markers. Human HCC samples with PVTT (n = 28) was analyzed through ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Transcript levels of mRNA in two cohorts from published database GEO (n = 60) and TCGA (n = 411) were downloaded to explore differentially expressed genes and functional enriched gene set. Evaluation of immune infiltration was estimated and validated from transcriptomic data in both cohorts through six immune deconvolution algorithms and in a high-resolution mode (CIBERSORTx). Survival analysis (Kaplan–Meier and multivariable Cox regression model) was performed to examine prognostic value of ACLY, related immune checkpoints and immune infiltration levels from TCGA cohort. LASSO regression was further conducted to determine a gene panel to further predict survival outcomes associated with ACLY. Results We identified a novel signature, ATP citrate lyase, through transcriptomic and metabolomic approaches. We demonstrated that the metabolism adaptations in both fatty acid and cholesterol biosynthesis triggered by ACLY oncogenic activation. We illustrated the crucial function of ACLY in lipogenesis and its potential interaction with immune microenvironment. CD276, a promising target in immune checkpoint blockade, showed correlation to ACLY and differential expression in ACLY risk classification. Combination of ACLY, CD276 and immune infiltration level and a novel ACLY-associated panel from a predictive model retrieved from published database validated the prognostic value to risk stratification in patients with HCC.ACLY blockade to counteract metabolic activation and immunosuppressive status of the tumor microenvironment highlighted attractive prospect for translational application. Conclusions We investigated ACLY and its indispensable role in metabolism, immune function and a prognostic gene panel in HCC. We anticipate that the multifaced role of ACLY may reveal the potential value for mechanistic research and combinational therapy, suggesting that the combination blockade of ACLY and immune checkpoints may work as a promising strategy.

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Section: Methodsmentioning

confidence: 99%

Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

Zhang

et al. 2021

Cancer Cell Int

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“…Human All Exon V7 bait panel (Agilent Technologies, Santa Clara, CA). Additionally, immune cell fraction was calculated by QuantiSeq [ 30 ] using this transcriptomic data.…”

Section: Methodsmentioning

confidence: 99%

Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas

et al. 2021

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Cancer/testis antigens (CTAs) are strongly expressed in some solid tumors but minimally expressed in normal tissue, making them appealing therapeutic targets. KK-LC-1 (CXorf61) has cytoplasmic expression in gastric, breast, and lung cancer. We characterized the molecular subtypes of non-small cell lung cancer (NSCLC) expressing KK-LC-1 to inform rational clinical trials of T-cell receptor therapy (TCR-T) targeting KK-LC-1. 9790 NSCLC tumors that underwent whole transcriptome sequencing (Illumina NovaSeq) and NextGen DNA sequencing (NextSeq, 592 Genes and NovaSEQ, WES) at Caris Life Sciences (Phoenix, AZ) were analyzed. Tumors were split into quartiles based on KK-LC-1 expression and pathological and molecular differences were investigated. Adenocarcinoma had significantly higher KK-LC-1 expression than squamous cell carcinoma (median, 3.25 vs. 1.17 transcripts per million (TPM), p < 0.0001). Tumors with the highest quartile of KK-LC-1 expression had a greater proportion of tumors with high tumor mutation burden (TMB) (≥10 mutations per megabase; 44% vs. 28% in Q1, p < 0.001). Increased KK-LC-1 expression was associated with increased M1 macrophage abundance. Higher levels of KK-LC-1 expression were seen in pan-wild type and KRAS mutated tumors and associated with high TMB. TCR-T therapy directed against KK-LC-1 should be considered in patients whose clinical features reflect these characteristics.

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“…The gene‐level abundance estimates from tximport were used as input to QuantiSeq, 15 which was invoked through the immunedeconv 16 package. QuantiSeq outputs estimated absolute fractions of 10 different immune cell populations; these absolute fractions allow for inter‐ and intrasample comparisons.…”

Section: Methodsmentioning

confidence: 99%

Immune checkpoint inhibitors in Wilms' tumor and Neuroblastoma: What now?

Valind

Gisselsson

2021

Cancer Reports

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Background: Therapeutic activation of tumor-infiltrating lymphocytes using monoclonal antibodies targeting PD1 or PD-L1 (immune checkpoint inhibitors-ICIs) has revolutionized treatment of specific solid tumors in adult cancer patients, and much hope has been placed on a similar effect in relapsed or refractory solid pediatric tumors. Recent clinical trials have disappointingly shown an almost nonexistent response rate, while case reports have demonstrated that some pediatric patients do achieve durable responses when treated with this type of drug.Aim: To elucidate this paradox, we mapped the landscape of expressed neoantigens as well as the levels of immune cell infiltration in the two most common extracranial solid pediatric tumors: Wilms tumor and neuroblastoma using state-of-the-art in silico analysis of a large cohort of patients with these tumors. Methods: By integration of whole exome sequencing and RNA-sequencing, we mapped the landscape of neoantigens in the TARGET cohorts for these diagnoses and correlated these findings with known genetic prognostic markers.Results: Our analysis shows that these tumors typically have much lower levels of expressed neoantigens than commonly seen in adult cancers, but we also identify subgroups with significantly higher levels of neoantigens. For neuroblastomas, the cases with higher levels of neoantigens were confined to the group without MYCN-amplification and for Wilms tumor restricted to the TP53-mutated cases. Furthermore, we demonstrate that neuroblastomas have an unexpectedly high level of CD8+ tumor-infiltrating lymphocytes, even when compared to adult tumor types where ICI is an approved treatment. Conclusion:These results could be important to consider when designing future clinical trials of ICI treatment in pediatric patients with relapsed or refractory solid tumors.

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Correction to: Molecular and pharmacological modulators of the tumor immune contexture revealed by deconvolution of RNA-seq data

Cited by 56 publications

References 1 publication

Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

Identification and integrative analysis of ACLY and related gene panels associated with immune microenvironment reveal prognostic significance in hepatocellular carcinoma

Molecular characterization of Kita-Kyushu lung cancer antigen (KK-LC-1) expressing carcinomas

Immune checkpoint inhibitors in Wilms' tumor and Neuroblastoma: What now?

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