Regulation of pancreatic cancer therapy resistance by chemokines

Gautam, Shailendra K.; Basu, Soumi; Dwivedi, Nidhi V.; Gulati, Mansi; Jain, Maneesh

doi:10.1016/j.semcancer.2022.08.010

Cited by 12 publications

(8 citation statements)

References 170 publications

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“…These findings further suggest that lncRNAs in risk model have favorable research value. Indeed, recent studies have reported that chemokine modifications and multiple lncRNAs can participate in multiple processes of tumor development [43,44]. Therefore, in order to explore whether risk models play a role in tumor and TME, we first performed GSEA and GO/KEGG enrichment analysis.…”

Section: Discussionmentioning

confidence: 99%

Novel chemokine related LncRNA signature correlates with the prognosis, immune landscape, and therapeutic sensitivity of esophageal squamous cell cancer

et al. 2023

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Background Esophageal squamous cell carcinoma (ESCC) is closely correlated with malignant biological characteristics and poor survival. Recently, chemokines have been reported to be involved in the progression of tumors, and they can also regulate the tumor microenvironment. However, it is unclear whether chemokine-related long noncoding RNAs (lncRNAs) affect the prognosis of ESCC. Methods We downloaded RNA-seq and clinical data from the Gene Expression Omnibus (GEO database. Chemokine-related lncRNAs were screened by differential analysis and Pearson correlation analysis. Then, prognosis-related lncRNAs were screened by using univariate COX regression, and risk models were constructed after the least absolute shrinkage and selection operator (LASSO) regression and multivariate COX regression. The predictive value of the signature was assessed using Kaplan–Meier test, time-dependent receiver operating characteristic (ROC) curves, decision curve analysis (DCA) and calibration curve. Moreover, a nomogram to predict patients’ 1-year 3-year and 5-year prognosis was constructed. Gene set enrichment analyses (GSEA), Gene Ontology/Kyoto Encyclopedia of Genes and Genomes (GO/KEGG), evaluation of immune cell infiltration, and estimation of drug sensitivity were also conducted. Results In this study, 677 chemokine-related lncRNAs were first obtained by differential analysis and Pearson correlation. Then, six chemokine-related lncRNAs were obtained by using univariate COX, LASSO and multivariate COX to construct a novel chemokine-related lncRNAs risk model. The signature manifested favorable predictive validity and accuracy both in the testing and training cohorts. The chemokine-related signature could classify ESCC patients into two risk groups well, which indicated that high-risk group exhibited poor prognostic outcome. In addition, this risk model played an important role in predicting signaling pathways, immune cell infiltration, stromal score, and drug sensitivity in ESCC patients. Conclusions These findings elucidated the critical role of novel prognostic chemokine-related lncRNAs in prognosis, immune landscape, and drug therapy, thus throwing light on prognostic evaluation and therapeutic targets for ESCC patients.

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Section: Discussionmentioning

confidence: 99%

Novel chemokine related LncRNA signature correlates with the prognosis, immune landscape, and therapeutic sensitivity of esophageal squamous cell cancer

et al. 2023

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“…Recent studies have reported that chemokines modifications and multiple lncRNAs can modulate the process of cancer immunity, including immune cell infiltration and immune resistance and activation in the TME, causing tumor progression [ 33 , 34 ]. Thus, to explore whether the risk model played a role in tumor and TME, we first performed GSEA and GSVA analyses.…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Chemokine-Related lncRNAs Signature Associated with Immune Landscape in Colon Adenocarcinoma

et al. 2022

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Chemokines have been reported to be involved in tumorigenesis and progression and can also modulate the tumor microenvironment. However, it is still unclear whether chemokine-related long noncoding RNAs (lncRNAs) can affect the prognosis of colon adenocarcinoma (COAD). We summarized chemokine-related genes and downloaded RNA-seq and clinical data from The Cancer Genome Atlas (TCGA) database. A total of 52 prognostic chemokine-related lncRNAs were screened by univariate Cox regression analysis; patients were grouped according to cluster analysis results. Lasso regression analysis was applied to determine chemokine-related lncRNAs to construct a risk model for further research. This study first investigated the differences between the prognosis and immune status of two chemokine-related lncRNAs clusters by consensus clustering. Then, using various algorithms, we obtained ten chemokine-related lncRNAs to construct a new prognostic chemokine-related lncRNAs risk model. The risk model’s predictive efficiency, validity, and accuracy were further validated and determined in the test and training cohorts. Furthermore, this risk model played a vital role in predicting immune cell infiltration, immune checkpoint gene expression, tumor mutational burden (TMB), immunotherapy score, and drug sensitivity in COAD patients. These findings elucidated the critical role of novel prognostic chemokine-related lncRNAs in prognosis, immune landscape, and drug therapy, thereby providing valuable insights for prognosis assessment and personalized treatment strategies for COAD patients.

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“…Besides, CXCR2 is not expressed in circulating T cells, yet its presence has been linked to macrophage infiltration [ 18 ]. Previous research also suggested that introduction of certain CXCRs may significantly improve the therapeutic effectiveness of CAR-T therapy in several different types of cancer [ 19 – 22 ]. Nevertheless, the potential beneficial functions of CXCR2 expression in CAR-T cells for the treatment of PDAC demand further investigation.…”

Section: Introductionmentioning

confidence: 99%

Ectopic CXCR2 expression cells improve the anti-tumor efficiency of CAR-T cells and remodel the immune microenvironment of pancreatic ductal adenocarcinoma

Dai,

Lin,

Wang

et al. 2024

Cancer Immunol Immunother

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Background Recent progressions in CAR-T cell therapy against pancreatic ductal adenocarcinoma (PDAC) remain disappointing, which are partially attributed to the immunosuppressive microenvironment including macrophage-mediated T cell repletion. Methods We first characterized the expression patterns of macrophage-relevant chemokines and identified CXCR2 as the key factor regulating T cell trafficking and tumor-specific accumulation in PDAC microenvironment. After that, we synthesized and introduced a CXCR2 expression cascade into Claudin18.2 CAR-T cells and compared the behaviors of CAR-T cells in vitro and in vivo. The therapeutic potential of CXCR2 CAR-T was evaluated in two different allogeneic models: subcutaneous allografts and metastatic PDAC models. Results The results showed that CXCR2 CAR-T not only reduced the size of allografted PDAC tumors, but also completely eliminated the formation of metastases. Lastly, we investigated the tumor tissues and found that expression of ectopic CXCR2 significantly improved tumor-targeted infiltration and residence of T cells and reduced the presence of MDSCs and CXCR2 + macrophages in PDAC microenvironment. Conclusion Our studies suggested that ectopic CXCR2 played a significant and promising role in improving the efficiency of CAR-T therapy against primary and metastatic PDAC and partially reversed the immune-suppressive microenvironment.

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Regulation of pancreatic cancer therapy resistance by chemokines

Cited by 12 publications

References 170 publications

Novel chemokine related LncRNA signature correlates with the prognosis, immune landscape, and therapeutic sensitivity of esophageal squamous cell cancer

Novel chemokine related LncRNA signature correlates with the prognosis, immune landscape, and therapeutic sensitivity of esophageal squamous cell cancer

A Novel Prognostic Chemokine-Related lncRNAs Signature Associated with Immune Landscape in Colon Adenocarcinoma

Ectopic CXCR2 expression cells improve the anti-tumor efficiency of CAR-T cells and remodel the immune microenvironment of pancreatic ductal adenocarcinoma

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