CXCL11 Correlates with Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis

Li, Yang; Han, Shukun; Wu, Baokang; Zhong, Chongli; Shi, Yu; Lv, Chao; Fu, Lei; Zhang, Yizhou; Lang, Qi; Liang, Zhiyun; Yu, Yang; Tian, Yu

doi:10.3389/fimmu.2022.951247

Cited by 23 publications

(20 citation statements)

References 33 publications

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“…5e, most chemokines in CDC42 gene set mutation patients were significantly higher than in CDC42 gene set wild type patients. Previous studies have reported that CXCL9, CXCL10 and CXCL11 can enhance T cell infiltration, thereby improving the therapeutic efficacy of ICI interventions[47–49]. The expression of CXCL13 can generate effector T cells and is closely associated with the response to ICIs treatment[50].…”

Section: Resultsmentioning

confidence: 99%

“…In TME, leukocyte fraction, lymphocyte fraction, TIL fraction and CD8 T cell levels were substantially higher in patients with CDC42 gene set mutations compared to those with CDC42 gene set wild type, indicating enhanced immunity. The increased expression of chemokines, such as CXCL9, CXCL10 and CXCL11, in patients with CDC42 gene set mutations can recruit more T cells into TME [47][48][49]. Additionally, higher expression of interleukins, like IL-10 and IL-21, in CDC42 gene set mutation patients promotes the survival of T cells.…”

Section: Discussionmentioning

confidence: 99%

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Mutation in CDC42 gene set as a response biomarker for immune checkpoint inhibitor therapy

Wang,

Zhang,

et al. 2023

Preprint

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BackgroundImmunotherapy has proven notably effective in treating tumors across diverse patient populations. However, some patients do not respond to immune checkpoint inhibitors (ICIs). Thus, there is a need for reliable biomarkers that can predict clinical responses to ICI treatment accurately.MethodsOur focus is on CDC42, a protein that stimulates multiple signaling pathways, promoting tumor growth. We hypothesize that its defective function may indicate a patient’s response to ICI therapy. We consider CDC42, along with its downstream binding and effector proteins, as a gene set. This is because their mutation could result in defective CDC42 function. We investigated the mutations in the CDC42 gene set as a potential biomarker for clinical benefits from ICI treatment. We also examined whether the combined use of a CDC42 inhibitor and ICI could enhance the efficacy of ICI.ResultsThe presence of mutations in the CDC42 gene set correlated with improved overall survival (OS: p = 2.9E-4) and progression-free survival (PFS: p = 2.92E-6). Furthermore, our analysis of immune response landscapes among different CDC42 gene set statuses supports its potential as a biomarker for ICI therapy. Animal experiments also revealed that combining the CDC42 inhibitor (ML141) with anti-PD-1 blockade can synergistically reduce tumor growth.ConclusionsOur study suggests that the CDC42 gene set could serve as a novel biomarker for the clinical response to ICI treatment. This finding also provides insight into the potential of combining ICI and CDC42 inhibitor use.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Mutation in CDC42 gene set as a response biomarker for immune checkpoint inhibitor therapy

Wang,

Zhang,

et al. 2023

Preprint

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“…Notably, the role of chemokines in the progression of LUAD is crucial, suggesting their potential importance in disease development. Multiple studies have indicated that the expression of members of the chemokine family is associated with poor prognosis in LUAD 60–62 . Indeed, the GSEA results suggest that patients in the high‐risk group have a poorer survival prognosis.…”

Section: Discussionmentioning

confidence: 99%

A novel iTreg‐related signature for prognostic prediction in lung adenocarcinoma

Zhang,

Li,

Yang

et al. 2023

Cancer Science

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Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Most patients are diagnosed at an advanced stage, therefore it is crucial to identify novel prognostic biomarkers for LUAD. As important regulatory cells, inducible regulatory T cells (iTregs) play a vital role in immune suppression and are important for the maintenance of immune homeostasis. This study explored the prognostic value and therapeutic effects of iTreg‐related genes in LUAD. Data for LUAD patients, including immune infiltration data, RNA sequencing data, and clinical features, were acquired from The Cancer Genome Atlas, Gene Expression Omnibus, and Tumor Immune Single‐cell Hub 2 databases. Immune‐related subgroups with different infiltration patterns and iTreg‐related genes were identified through univariate and multivariate Cox regression analyses and weighted correlation network analysis. Functional enrichment analyses were performed to explore the underlying mechanisms of iTreg‐related genes. A prognostic risk signature was constructed using Cox regression analysis with the least absolute shrinkage and selection operator penalty. The ESTIMATE algorithm was applied to determine the immune status of LUAD patients. We applied the constructed signature to predict chemosensitivity and performed single‐cell RNA sequencing analysis. The infiltration of iTregs was identified as an independent factor for predicting patient outcomes. We constructed a prognostic signature based on seven iTreg‐related genes (GIMAP5, SLA, MS4A7, ZNF366, POU2AF1, MRPL12, and COL5A1), which was applied to subdivide patients into high‐ and low‐risk subgroups. Our results revealed that patients in the iTreg‐related low‐risk subgroup had a better prognosis and possibly greater sensitivity to traditional chemotherapy. Our study provides a novel iTreg‐related signature to elucidate the mechanisms underlying LUAD prognosis and promote individualized chemotherapy treatment.

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“…We used UALCAN, an interactive web resource ( http://ualcan.path.uab.edu/index.html ) which provides cancer OMICS data, including TCGA (The Cancer Genome Atlas) [ 22 ] and MET500 database [ 23 ], to screen the top 50 overexpressed genes and to analyze the expression of YKL-40 (CHI3L1) in STAD patients. TIMER (Tumor Immune Estimation Resource) [ 24 ] ( https://cistrome.shinyapps.io/timer ) provides survival module between gene expression and clinical outcome in a multivariable Cox proportional hazard model, and has the functions to draw Spearman's correlation curves and to provide pair-wise gene expression correlation analysis for given sets of TCGA and/or GTEx (the Genotype-Tissue Expression) database [ 25 ]. Using TIMER, we performed the correlation analysis between ADRB genes (ADRB1, ADRB2, and ADRB3) and CHI3L1, and analyzed the correlations of NGF expression and macrophage infiltration with the cumulative survival rate.…”

Section: Methodsmentioning

confidence: 99%

Sympathetic nerve infiltration promotes stomach adenocarcinoma progression via norepinephrine/β2-adrenoceptor/YKL-40 signaling pathway

Qi¹,

Yang²,

Lan³

et al. 2022

Heliyon

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CXCL11 Correlates with Immune Infiltration and Impacts Patient Immunotherapy Efficacy: A Pan-Cancer Analysis

Cited by 23 publications

References 33 publications

Mutation in CDC42 gene set as a response biomarker for immune checkpoint inhibitor therapy

Mutation in CDC42 gene set as a response biomarker for immune checkpoint inhibitor therapy

A novel iTreg‐related signature for prognostic prediction in lung adenocarcinoma

Sympathetic nerve infiltration promotes stomach adenocarcinoma progression via norepinephrine/β2-adrenoceptor/YKL-40 signaling pathway

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