LC3 and NLRC5 interaction inhibits NLRC5-mediated MHC class I antigen presentation pathway in endometrial cancer

Zhan, Lei; Zhang, Junhui; Zhang, Jing; Liu, Xiaojing; Zhu, Suding; Shi, Yuchuan; He, Yu; Wang, Wenyan; Fan, Yijun; Tang, Zhichen; Chen, Guo; Wei, Bing; Cao, Yunxia

doi:10.1016/j.canlet.2021.12.031

Cited by 26 publications

(25 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, compared with any single-drug group, the combined drug groups showed stronger killing power ( P < 0.05). To further verify whether KU combined with matrine can enhance antitumor efficacy in vivo , we conducted animal experiments [ 28 ]. Both tumor volume and tumor weight in LPS+KU+Matrine group were smaller than those in LPS, LPS+KU0063794 and LPS+matrine groups.…”

Section: Discussionmentioning

confidence: 99%

Matrine Combined with Mammalian Target of Rapamycin Inhibitor Enhances Anti-Tumor Efficacy of dendritic cell Vaccines in hepatocellular carcinoma

Zhou

Zhang³

et al. 2022

Bioengineered

View full text Add to dashboard Cite

Dendritic cells (DCs), as the most important antigen-presenting cells, play a crucial role in T cell activation. The latest research showed that inhibition of the mammalian target of rapamycin (mTOR) could enhance DCs maturation, promoting antigen presentation. Matrine has been identified as one of the key alkaloids isolated from the roots of Sophora flavescens . In present study, we combined matrine and mTOR inhibitor KU0063794 to observe the DCs functions, especially the antigen presentation ability. DCs were activated by phosphate-buffered saline (PBS), lipopolysaccharide (LPS), LPS+KU0063794, LPS+Matrine, and LPS+KU0063794+Matrine. The surface markers in DCs, proliferation of T cells and cytokines were detected by flow cytometry, cell counting kit-8 (CCK-8) and enzyme-linked immunosorbent assay (ELISA), respectively. The lactate dehydrogenase (LDH) release test was used to detect the antitumor efficacy. The tumor growth curves were plotted by calculating tumor volume. The apoptosis was detected by Terminal-deoxynucleoitidyl Transferase-Mediated Nick End Labeling (TUNEL) method. Matrine combined with KU0063794 could enhance the maturity of DCs, T cells proliferation and cytokines secretion ( P < 0.05). The cytotoxic T lymphocytes (CTL) killing efficacy of LPS+KU0063794+Matrine group was higher than other groups (P < 0.05). In vivo , the tumor weights and volumes in LPS+KU0063794+Matrine group were lower than other groups. The detections of tumor apoptosis were increased in LPS+KU0063794+Matrine group ( P < 0.05). DC vaccine with mTOR inhibitor and matrine could significantly improve the efficacy of antitumor immunity in vitro and vivo. These findings illustrated that mTOR inhibitor and matrine, as two immunomodulators, could enhance DC activation and differentiation.

show abstract

Section: Discussionmentioning

confidence: 99%

Matrine Combined with Mammalian Target of Rapamycin Inhibitor Enhances Anti-Tumor Efficacy of dendritic cell Vaccines in hepatocellular carcinoma

Zhou

Zhang³

et al. 2022

Bioengineered

View full text Add to dashboard Cite

show abstract

“…It was known that RNF135 regulated the expression of IFN, and it participated in the RIG-I signal pathway by targeting RIG-I ( Lai et al, 2019 ). NLRC5 could combine with LC3 to mediate MHC class I antigen presentation pathway ( Zhan et al, 2022 ). MAVS mediated antiviral innate immunity ( Zhang et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Systematic analysis of virus nucleic acid sensor DDX58 in malignant tumor

Huang

Jin

et al. 2022

Front. Microbiol.

View full text Add to dashboard Cite

IntroductionIn December 2019, a novel epidemic of coronavirus pneumonia (COVID-19) was reported，and population-based studies had shown that cancer was a risk factor for death from COVID-19 infection. However, the molecular mechanism between COVID-19 and cancer remains indistinct. In this paper, we analyzed the nucleic acid sensor (DDX58) of SARS-CoV-2 virus, which is a significant gene related to virus infection. For purpose of clarifying the characteristics of DDX58 expression in malignant tumors, this study began to systematically analyze the DDX58 expression profile in the entire cancer type spectrum.MethodsUsing TCGA pan-cancer database and related data resources, we analyzed the expression, survival analysis, methylation expression, mutation status, microsatellite instability (MSI), immune related microenvironment, gene related network, function and drug sensitivity of DDX58.ResultsThe expression level of DDX58 mRNA in most cancers was higher than the expression level in normal tissues. Through TIMER algorithm mining, we found that DDX58 expression was closely related to various levels of immune infiltration in pan-cancer. The promoter methylation level of DDX58 was significantly increased in multiple cancers. In addition, abnormal expression of DDX58 was related to MSI and TMB in multiple cancers, and the most common type of genomic mutation was “mutation.” In the protein–protein interaction (PPI) network, we found that type I interferon, phagocytosis, ubiquitinase, and tumor pathways were significantly enriched. Finally, according to the expression of DDX58 indicated potential sensitive drugs such as Cediranib, VE−821, Itraconazole, JNJ−42756493, IWR−1, and Linsitinib.DiscussionIn conclusion, we had gained new insights into how DDX58 might contribute to tumor development, and DDX58 could be used as an immune-related biomarker and as a potential immunotherapeutic target for COVID-19 infected cancer patients.

show abstract

“…However, autophagy also results in antigen damage, which impairs the immune response. DAMPs and pathogen-associated molecular patterns can initiate autophagy, then autophagosomes will eradicate these molecules to maintain immunological homeostasis ( 99 ). Based on its role in the phagocytosis of antigens, autophagy is a potential protective mechanism for tumor cells against ICD-induced immune responses ( 99 ).…”

Section: Altered Autophagy Burns Up the Immunosuppressive Tme To Prom...mentioning

confidence: 99%

“…Furthermore, autophagy inhibition possibly enhances MHC-I expression on the surface of DC and tumor cells for reducing endocytosis and degradative function, thereby promoting activation and migration of DC, and attraction of CD8 + T cells. Ultimately, these ignite the immunosuppressive TME and overcome resistance to the immune checkpoint blockade (ICB) ( 99 , 103 ). Inhibiting the selective autophagy of MHC-I —this was mediated by the autophagic cargo receptor NBR1— increased MHC-I expression in tumor cells ( 65 ).…”

Section: Altered Autophagy Burns Up the Immunosuppressive Tme To Prom...mentioning

confidence: 99%

“…Inhibiting the selective autophagy of MHC-I —this was mediated by the autophagic cargo receptor NBR1— increased MHC-I expression in tumor cells ( 65 ). In endometrial cancer, overexpression of LC3 constrained the MHC-I transactivator nucleotide-binding oligomerization domain-like receptor family caspase-containing recruitment domain 5 (NLRC5), a transcriptional regulator of the MHC-I gene, which then decreased the expression of MHC-I ( 99 ). Blocking tumor-derived progranulin destroys autophagosomes, restoring MHC-I expression.…”

Section: Altered Autophagy Burns Up the Immunosuppressive Tme To Prom...mentioning

confidence: 99%

See 1 more Smart Citation

Regulation of autophagy fires up the cold tumor microenvironment to improve cancer immunotherapy

Jin

Sun²,

Wang³

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Immunotherapies, such as immune checkpoint inhibitors (ICIs) and chimeric antigen receptor (CAR) T cells, have revolutionized the treatment of patients with advanced and metastatic tumors resistant to traditional therapies. However, the immunosuppressed tumor microenvironment (TME) results in a weak response to immunotherapy. Therefore, to realize the full potential of immunotherapy and obstacle barriers, it is essential to explore how to convert cold TME to hot TME. Autophagy is a crucial cellular process that preserves cellular stability in the cellular components of the TME, contributing to the characterization of the immunosuppressive TME. Targeted autophagy ignites immunosuppressive TME by influencing antigen release, antigen presentation, antigen recognition, and immune cell trafficking, thereby enhancing the effectiveness of cancer immunotherapy and overcoming resistance to immunotherapy. In this review, we summarize the characteristics and components of TME, explore the mechanisms and functions of autophagy in the characterization and regulation of TME, and discuss autophagy-based therapies as adjuvant enhancers of immunotherapy to improve the effectiveness of immunotherapy.

show abstract

LC3 and NLRC5 interaction inhibits NLRC5-mediated MHC class I antigen presentation pathway in endometrial cancer

Cited by 26 publications

References 43 publications

Matrine Combined with Mammalian Target of Rapamycin Inhibitor Enhances Anti-Tumor Efficacy of dendritic cell Vaccines in hepatocellular carcinoma

Matrine Combined with Mammalian Target of Rapamycin Inhibitor Enhances Anti-Tumor Efficacy of dendritic cell Vaccines in hepatocellular carcinoma

Systematic analysis of virus nucleic acid sensor DDX58 in malignant tumor

Regulation of autophagy fires up the cold tumor microenvironment to improve cancer immunotherapy

Contact Info

Product

Resources

About