Understanding Suboptimal Response to Immune Checkpoint Inhibitors

Zhu, Mojun; Zhang, Henan; Pedersen, Katrina; Foster, Nathan R.; Jaszewski, Brandy L.; Liu, Xin; Hirdler, Jacob B.; An, Zesheng; Bekaii‐Saab, Tanios; Halfdanarson, Thorvardur R.; Boland, Patrick M.; Yan, Yiyi; Hubbard, Joleen H; Wee, Wen; Yoon, Harry H.; Revzin, Alexander; Fernández-Zapico, Martín E.; Overman, Michael J.; McWilliams, Robert R.; Dong, Haidong

doi:10.1002/adbi.202101319

Cited by 5 publications

(3 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The tumor microenvironment (TME) is a multifaceted cytosolic environment that both limits tumor development (25)(26)(27) and plays a key role in tumor progression and therapeutic response (28)(29)(30)(31). In lung adenocarcinoma (LUAD), they evaluated the correlation between the m6A-related lncRNA model and immunotherapy biomarkers, and the m6A-based classifier index can be used as a predictor of TIDE and TMB (32).…”

Section: Introductionmentioning

confidence: 99%

Identified Gefitinib Metabolism-Related lncRNAs can be Applied to Predict Prognosis, Tumor Microenvironment, and Drug Sensitivity in Non-Small Cell Lung Cancer

Gao

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

Gefitinib has shown promising efficacy in the treatment of patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). Molecular biomarkers for gefitinib metabolism-related lncRNAs have not yet been elucidated. Here, we downloaded relevant genes and matched them to relevant lncRNAs. We then used univariate, LASSO, and multivariate regression to screen for significant genes to construct prognostic models. We investigated TME and drug sensitivity by risk score data. All lncRNAs with differential expression were selected for GO/KEGG analysis. Imvigor210 cohort was used to validate the value of the prognostic model. Finally, we performed a stemness indices difference analysis. lncRNA-constructed prognostic models were significant in the high-risk and low-risk subgroups. Immune pathways were identified in both groups at low risk. The higher the risk score the greater the value of exclusion, MDSC, and CAF. PRRophetic algorithm screened a total of 58 compounds. In conclusion, the prognostic model we constructed can accurately predict OS in NSCLC patients. Two groups of low-risk immune pathways are beneficial to patients. Gefitinib metabolism was again validated to be related to cytochrome P450 and lipid metabolism. Finally, drugs that might be used to treat NSCLC patients were screened.

show abstract

Section: Introductionmentioning

confidence: 99%

Identified Gefitinib Metabolism-Related lncRNAs can be Applied to Predict Prognosis, Tumor Microenvironment, and Drug Sensitivity in Non-Small Cell Lung Cancer

Gao

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

show abstract

“…5) Ma, X. et al found that CD8 (+) T cells induce lipid peroxidation and ferroptosis mediated by CD36, resulting in reduced production of cytotoxic factors and antitumor ability of CD8 (+) T cells. Targeting CD36 restores the ability of CD8 (+) T cells to participate in tumor immunotherapy (Ma et al, 2021;Aksoylar and Patsoukis, 2022;Zhu et al, 2022).…”

Section: Ferroptosis and Tumor Immunotherapymentioning

confidence: 99%

The Mechanisms of Ferroptosis and the Applications in Tumor Treatment: Enemies or Friends?

Tan

Kong

Xian

et al. 2022

Front. Mol. Biosci.

View full text Add to dashboard Cite

Ferroptosis, as a newly discovered non-apoptotic cell death mode, is beginning to be explored in different cancer. The particularity of ferroptosis lies in the accumulation of iron dependence and lipid peroxides, and it is different from the classical cell death modes such as apoptosis and necrosis in terms of action mode, biochemical characteristics, and genetics. The mechanism of ferroptosis can be divided into many different pathways, so it is particularly important to identify the key sites of ferroptosis in the disease. Herein, based on ferroptosis, we analyze the main pathways in detail. More importantly, ferroptosis is linked to the development of different systems of the tumor, providing personalized plans for the examination, treatment, and prognosis of cancer patients. Although some mechanisms and side effects of ferroptosis still need to be studied, it is still a promising method for cancer treatment.

show abstract

“…Some studies have shown that CX3CL1 can promote immune cell infiltration and activation, thereby inhibiting tumorigenesis and regulating inflammatory response [ 17 , 18 ]. CX3CR1 inhibitors have been shown to enhance the efficacy of immunotherapy in cancer treatment [ 19 ]. High expression of CX3CL1 may lead to excessive activation of immune cells and tissue damage in IBD and RA [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro

Feng,

Zhu,

Qiao

et al. 2023

J Transl Med

View full text Add to dashboard Cite

Background Ankylosing spondylitis (AS) is an autoimmune disease with a genetic correlation and is characterized by inflammation in the axial skeleton and sacroiliac joints. Many AS patients also have inflammatory bowel diseases (IBD), but the underlying causes of intestinal inflammation and osteoporosis in AS are not well understood. CX3CL1, a protein involved in inflammation, has been found to be up-regulated in AS patients and AS-model mice. Methods The authors investigated the effects of CX3CL1 on AS by studying its impact on macrophage polarization, inflammation factors, and osteoclast differentiation. Furthermore, the effects of inhibiting the NF-κB pathway and blocking CX3CL1 were assessed using BAY-117082 and anti-CX3CL1 mAb, respectively. AS model mice were used to evaluate the effects of anti-CX3CL1 mAb on limb thickness, spine rupture, and intestinal tissue damage. Results The authors found that CX3CL1 increased the expression of M1-type macrophage markers and inflammation factors, and promoted osteoclast differentiation. This effect was mediated through the NF-κB signaling pathway. Inhibition of the NF-κB pathway prevented M1-type macrophage polarization, reduced inflammation levels, and inhibited osteoclast differentiation. Injection of anti-CX3CL1 mAb alleviated limb thickness, spine rupture, and intestinal tissue damage in AS model mice by inhibiting M1-type macrophage polarization and reducing intestinal tissue inflammation. Conclusions The study demonstrated that up-regulated CX3CL1 promotes M1-type macrophage polarization and osteoclast differentiation through the NF-κB signaling pathway. Inhibition of this pathway and blocking CX3CL1 can alleviate inflammation and bone destruction in AS. These findings contribute to a better understanding of the pathogenesis of AS and provide a basis for clinical diagnosis and treatment.

show abstract

Understanding Suboptimal Response to Immune Checkpoint Inhibitors

Cited by 5 publications

References 37 publications

Identified Gefitinib Metabolism-Related lncRNAs can be Applied to Predict Prognosis, Tumor Microenvironment, and Drug Sensitivity in Non-Small Cell Lung Cancer

Identified Gefitinib Metabolism-Related lncRNAs can be Applied to Predict Prognosis, Tumor Microenvironment, and Drug Sensitivity in Non-Small Cell Lung Cancer

The Mechanisms of Ferroptosis and the Applications in Tumor Treatment: Enemies or Friends?

CX3CL1 promotes M1 macrophage polarization and osteoclast differentiation through NF-κB signaling pathway in ankylosing spondylitis in vitro

Contact Info

Product

Resources

About