{"title":"Function of steroid receptor coactivators (SRCs) in T cells and cancers: Implications for cancer immunotherapy","authors":"Wencan Zhang, Xu Cao, Hongmin Wu, Xiancai Zhong, Yun Shi, Zuoming Sun","doi":"10.1615/critrevimmunol.2024051613","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051613","url":null,"abstract":"Steroid receptor coactivator (SRC) family members (SRC1, SRC2 and SRC3) are transcriptional co-regulators. SRCs orchestrate gene transcription by inducing transactivation of nuclear receptors and other transcription factors. Overexpression of SRCs is widely implicated in a range of cancers, especially hormone-related cancers. As coactivators, SRCs regulate multiple metabolic pathways involved in tumor growth, invasion, metastasis, and chemo-resistance. Emerging evidence in recent years suggest that SRCs also regulate maturation, differentiation, and cytotoxicity of T cells by controlling metabolic activities. In this review, we summarize the current understanding of the function of SRCs in T cells as well as cancer cells. Importantly, the controversies of targeting SRCs for cancer immunotherapy as well as possible reconciliation strategies are also discussed.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"12 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140069872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"KIAA1429 induces the m6A modification of LINC01106 to enhance the malignancy of lung adenocarcinoma cell via JAK/STAT3 pathway","authors":"Di Xu, Ziming Wang, Fajiu Li","doi":"10.1615/critrevimmunol.2024052728","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052728","url":null,"abstract":"Background: Sustained expression of LINC01106 in tumors is crucial for malignant phenotype of tumor cells; Nevertheless, LINC01106’s mechanisms and clinical effects in lung adenocarcinoma (LUAD) is confined. This report focus on reveal the effect of vir-like m6A methyltransferase associated (KIAA1429)-mediated N6-methyladenosine (m6A) modification to steady LINC01106 expression on LUAD progression.\u0000Methods: qRT-PCR was conducted to clarify the LINC01106 and KIAA1429 levels in LUAD tissues. LINC01106’s and KIAA1429’s functional roles were analyzed utilizing Transwell, EdU as well as CCK-8 assays. Xenograft was cconducted to verify the function of silencing LINC01106 in tumor growth. The regulatory role between LINC01106 was investigated using MeRIP, qRT-PCR as well as Actinomycin D assay. Key proteins of JAK/STAT3 (JAK2, STAT3) pathway were revealed via western blotting.\u0000Results: LINC01106 and KIAA1429 were high-expressed in LUAD, and LINC01106 were interconnected with high tumor grade, stage, and poor prognosis. Data revealed LINC01106 inhibition reduced LUAD cell proliferation, invasion as well as migration, and restrained LUAD cell tumorigenicity. Additionally, phosphorylated JAK2, STAT3 levels were reduced by LINC01106 silencing. LINC01106 was mediated by KIAA1429 to enhance its m6A modification and expression in LUAD cells. Moreover, KIAA1429 promotion abolished the malignant phenotypic suppression induced by LINC01106 lowexpression in LUAD cells.\u0000Conclusion: This research revealed LINC01106 m6A modification was enhanced by KIAA1429 to play the promotive role in LUAD development. The results may conduce to the comprehending of the act of KIAA1429-m6A-LINC0110","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"18 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139977763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Oral Cancer: Past, present and future of NK cell-based cancer immunotherapy","authors":"Kawaljit Kaur, Anahid Jewett","doi":"10.1615/critrevimmunol.2024052389","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052389","url":null,"abstract":"Despite advancements in the field of cancer therapeutics the five-year survival rate remains low in oral cancer patients. There, the effective therapeutics are needed to control the disease. Also, several studies including ours have shown severely suppressed function and number of NK cells in oral cancer patients. In this review, we discuss the approach to inhibit the tumor growth and metastasis by direct killing or NK cell-mediated tumor differentiation. This review also provides the overview on supercharging NK cells using osteoclasts and probiotic bacteria, and their efficacy as cancer immunotherapeutic in humanized-BLT mice.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"12 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754824","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of p-estrogen receptor at serine on its function and breast growth","authors":"Yuan Liang, Junhui Qin, Tiancheng Ma, Tong Yang, Zhenyu Ke, Ruian Wang","doi":"10.1615/critrevimmunol.2024052499","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052499","url":null,"abstract":"Background: Estrogen receptor (ER) signaling plays an important role in the development and functional differentiation of breast and participates in the process of breast cancer. Activated ER can affect various aspects of the cell’s behavior, including proliferation, via modulating the expression of many downstream target genes. Phosphorylation is one of the activation pathways of ER. However, the relationship between estrogen receptor phosphorylation sites and breast development and carcinogenesis is not clear.\u0000Methods: Using Crisper-Cas9 gene editing technology, we constructed ER S309A mutant mice. Using carmine staining of mammary gland of mice at different developmental stages, we examined breast development of ER S309Amice. Using HE staining of vaginal smears of mice at the same time for 5 consecutive days, we measured the vaginal epithelial keratinocytes.\u0000Results: We established ER S309A mutant mice and observed breast defects in ER S309A mice. In addition, we observed decreased reproductive ability, estrous cycle disorder in ER S309A mice. And number of vaginal epithelial keratinocytes in the estrous cycle of ER S309A mice was decreased.\u0000Conclusion: These results suggest that phosphorylation site of ER at serine 309 is important for ER function and breast development.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"6 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139918547","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The value of systemic immune-inflammation index and T cell subsets in the severity and prognosis of sepsis","authors":"Hao Zhou","doi":"10.1615/critrevimmunol.2024051413","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051413","url":null,"abstract":"Systemic immune-inflammation index (SII) and T cell subsets show involvement in mortality risk in septic patients, and we explored their predictive value in sepsis. Subjects were categorized into the Sepsis (SP)/Septic Shock (SSP)/Septic Shock (SPS) groups. T cell subsets [T-helper (Th)1, Th2, regulatory T cells (Treg), Th17]/platelets (PLT)/neutrophils (NEU)/lymphocytes (LYM)/C-reactive protein (CRP)/procalcitonin (PCT)/interleukin (IL)-4/IL-10/fibrinogen (FIB) were measured by an automatic blood biochemical analyzer/flow cytometry/Countess II FL automatic blood cell analyzer, with SII calculated. The correlations between SII/T cell subsets with Acute Physiology and Chronic Health Evaluation (APACH) II/Sequential Organ Failure Assessment (SOFA) scores and the predictive value of SII/Th1/Th2 for septic diagnosis/prognosis were analyzed using Spearman/ROC curve/Kaplan-Meier. The three groups varied in PLT/NEU/LYM/CRP/PCT/IL-4/IL-10/FIB levels and APACH II/SOFA scores. Compared with the SP group, the other two groups showed elevated APACH II/SOFA scores and SII/Th1/Th2/Th17/Treg levels. SII/Th1/Th2 levels significantly positively correlated with APACH II/SOFA scores. SII/Th1/Th2 levels had high predictive value for septic diagnosis/prognosis, with their combination exhibiting higher predictive value. Septic patients with high SII/Th1/Th2 levels exhibited lower survival rates. Altogether, SII, Th1, and Th2 had good predictive value for the diagnosis and prognosis of patients with varying severity of sepsis, with their high levels increasing mortality in septic patients.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"2 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139663580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jianghui Wang, Shufang Ni, Kai Zheng, Yan Zhao, peihong zhang, Hong Chang
{"title":"Phillygenin alleviated arthritis through the inhibition of NLRP3 inflammasome and Ferroptosis by AMPK","authors":"Jianghui Wang, Shufang Ni, Kai Zheng, Yan Zhao, peihong zhang, Hong Chang","doi":"10.1615/critrevimmunol.2024051467","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051467","url":null,"abstract":"Background: We investigated the potential arthritis-inducing effects of Phillygenin and its underlying mechanisms.\u0000Methods: RAW264.7 cells were stimulated with lipopolysaccharide to induce inflammation.\u0000Results: Phillygenin was found to reduce arthritis score, histopathological changes, paw edema, spleen index, and ALP levels in a dose-dependent manner in a model of arthritis. Additionally, Phillygenin was able to decrease levels of inflammation markers in serum samples of mice with arthritis and also inhibited inflammation markers in the cell supernatant of an in vitro model of arthritis. Phillygenin increased cell viability and JC-1 disaggregation, enhanced calcien-AM/CoCl2, reduced LDH activity levels and IL-1α levels, and inhibited Calcein/PI levels and iron concentration in an in vitro model. Phillygenin was also found to reduce ROS-induced oxidative stress and Ferroptosis, and suppress the NLRP3 inflammasome in both in vivo and in vitro models through AMPK. In the in vivo model, Phillygenin was observed to interact with AMPK protein.Conclusions: These findings suggest that Phillygenin may be a potential therapeutic target for preventing arthritis by inhibiting NLRP3 inflammasome and Ferroptosis through AMPK. This indicates that Phillygenin could have disease-modifying effects on arthritis.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"16 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tu Nguyen, Po-Chun Chen, Janet Pham, Kawaljit Kaur, Steven Raman, Anahid Jewett, Jason Chiang
{"title":"The Current and Future States of Natural Killer Cell-Based Immunotherapy in Hepatocellular Carcinoma","authors":"Tu Nguyen, Po-Chun Chen, Janet Pham, Kawaljit Kaur, Steven Raman, Anahid Jewett, Jason Chiang","doi":"10.1615/critrevimmunol.2024052486","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052486","url":null,"abstract":"Natural killer (NK) cells are innate lymphoid cells that exhibit high levels of cytotoxicity against NK-specific targets, produce various cytokines, and interact with T cells, B cells, and dendritic cells to effectively serve as frontliners of the innate immune system. Moreover, NK cells constitue the second most frequent immune cell in the liver. These properties have drawn significant attention towards leveraging NK cells in treating liver cancer, especially hepatocellular carcinoma (HCC), which accounts for 75% of all liver cancer and is the fourth leading cause of cancer-related death worldwide. Notable anti-cancer functions of NK cells against HCC include activating antibody-dependent cell cytotoxicity (ADCC), facilitating Gasdermin E-mediated pyroptosis of HCC cells, and initiating an antitumor response via the cGAS-STING signaling pathway. In this review, we describe how these mechanisms work in the context of HCC. We will then discuss the existing preclinical and clinical studies that leverage NK cell activity to create single and combined immunotherapies.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"25 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139754891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and Nuances of Precision Molecular Engineering for Hodgkin's Disease to a Gene Therapeutic Approach","authors":"Muhammad Imran Qadir, Bilal Ahmed, Nadir Hussain","doi":"10.1615/critrevimmunol.2024052378","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024052378","url":null,"abstract":"Gene therapy is a particularly useful treatment for nervous system genetic illnesses, including those induced especially by infectious organisms and antigens, and is being utilized to treat Hodgkin's disease. Due to the possible clonal relationship between both disorders, immunotherapy directed against CD20 positive cells may be a more effective treatment in patients with persistent HD and NHL.HL growth can be inhibited both in vitro and in vivo by AdsIL-13Ralpha2. High-dose treatment combined with stem cell transplantation has been effective in treating HIV-negative lymphoma that has progressed to high-risk or relapsed illness. For therapy, LMP2-specific CTL will be used. Furthermore, it is possible to view the cytotoxicity of genetically modified adenoviruses that express proteins such as p27Kip1, p21Waf1, and p16INK4A as a foundational element for (2;5)-derived ALCL genetic treatment for Hodgkin's disease","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139656290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Identification of a Novel Five-Gene Prognostic Model for Laryngeal Cancer Associated with Mitophagy Using Integrated Bioinformatics Analysis and Experimental Verification","authors":"Dong Song, Lun Dong, Mei Wang, Xiaoping Gao","doi":"10.1615/critrevimmunol.2024051787","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2024051787","url":null,"abstract":"Laryngeal cancer (LC) is a prevailing tumor with a high mortality rate. The pivotal role of mitophagy in LC is acknowledged; however, a comprehensive analysis of the corresponding genes has not been conducted. In the present study, we proposed a prognostic model consisting of mitophagy-related genes in LC. Clinical information and transcriptome profiling of patients with LC and mitophagy-related genes were retrieved from open-source databases. Gene set variation analysis (GSVA) and Weighted Gene Co-expression Network Analysis (WGCNA) were used to identify core mitophagy-related genes and construct gene co-expression networks. Functional enrichment analysis was employed to analyze the enriched regulatory pathways of the mitophagy-related genes. Kaplan-Meier curves (KM), Cox, and LASSO regression were applied to explore their prognostic effects. Finally, quantitative real-time PCR (RT-qPCR) further verified the bioinformatics prediction. A total of 45 genes related to mitochondrial pathways was collected. GSVA analysis demonstrated that these genes in tumor samples mainly referred to the mitochondrial pathway. Among these genes, five mitophagy-related-gene signatures (<i>CERCAM, CHPF, EPHX3, EXT2</i>, and <i>MED15</i>) were further identified to construct the prognostic model. KM and Cox regression analyses indicated that this model had an accurate prognostic prediction for LC. RT-qPCR showed that <i>CERCAM, CHPF, EXT2</i>, and <i>MED15</i> expression were upregulated, and <i>EPHX3</i> level was decreased in LC cells. The present study established a five-mitophagy-related-gene model that can predict the prognosis of LC patients, thus laying the foundation for a better understanding and potential advancements in clinical treatments for LC.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"296 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140805096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Study of Therapeutic Mechanisms of Bupi Yichang Formula against Colon Cancer Based on Network Pharmacology, Machine Learning, and Experimental Verification","authors":"Juan Du","doi":"10.1615/critrevimmunol.2023051509","DOIUrl":"https://doi.org/10.1615/critrevimmunol.2023051509","url":null,"abstract":"Bupi Yichang formula (BPYCF) has shown the anti-cancer potential; however, its effects on colon cancer and the mechanisms remain unknown. This study intended to explore the effects of BPYC on colon cancer and its underlying mechanisms. BPYCF-related and colon cancer-related targets were acquired from public databases, followed by differentially expressed genes (DEG) identification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed using clusterProfiler. A protein-protein interaction (PPI) network was constructed using STRING database. CytoHubba and MCODE to screen the hub targets. A diagnostic model was built using random forest algorithm. Molecular docking was conducted using PyMOL and AutoDock. High-performance liquid chromatograph-mass spectrometry (HPLC-MS) analysis and <i>in vitro</i> validation were performed. Forty-six overlapping targets of BPYCF-related, colon cancer-related targets, and DEGs were obtained. GO and KEGG analyses showed that the targets were mainly enriched in response to lipopolysaccharide, neuronal cell body, protein serine/threonine/tyrosine, as well as C-type lectin receptor, NOD-like receptor, and TNF signaling pathways. Five targets were identified as the pivotal targets, among which, NOS3, CASP8, RIPK3, and TNFRSF10B were stably docked with the core active component, naringenin. Naringenin was also identified from the BPYCF sample through HPLC-MS analysis. <i>In vitro</i> experiments showed that BPYCF inhibited cell viability, reduced NOS3 expression, and elevated CASP8, RIPK3, and TNFRSF10B expression in colon cancer cells. BPYCF might treat colon cancer mainly by regulating NOS3, CASP8, RIPK3, and TN-FRSF10B. This study first revealed the therapeutic effects and mechanisms of BPYCF against colon cancer, paving the path for the development of targeted therapeutic strategies for this cancer in the clinic.","PeriodicalId":55205,"journal":{"name":"Critical Reviews in Immunology","volume":"1 1","pages":""},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139421559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}