Immunobiology最新文献

{"title":"Downregulating LKB1 in bone marrow mesenchymal stem cells could inhibit CD4+ T cell proliferation via the PD-1/PD-L1 signaling pathway","authors":"Yaqin Zhang ,&nbsp;Jingyi Ren ,&nbsp;Zhongxian Liao,&nbsp;Xiaoyu Li,&nbsp;Chunying Zhang,&nbsp;Bihan Huang,&nbsp;Yingping Cao,&nbsp;Jiadi Chen","doi":"10.1016/j.imbio.2024.152856","DOIUrl":"10.1016/j.imbio.2024.152856","url":null,"abstract":"<div><h3>Background</h3><div>Our previous research has shown that LKB1 in amniotic mesenchymal stem cells (MSCs) serves as a vital regulator of regulatory T cell differentiation and T cell proliferation, which may have a similar role in bone marrow MSCs (BMMSCs). Therefore, we investigated the role of LKB1 in BMMSCs for regulating CD4⁺ T cell proliferation in the bone micro-environment of AML.</div></div><div><h3>Methods</h3><div>RT-PCR was used to assessed LKB1 expression in BMMSCs derived from AML patients and healthy controls. Subsequently, LKB1 was knocked down in the BMMSCs line HS-5 (HS-5-LKB1^KD). Co-cultures in vitro were established to analyze the effect of HS-5-LKB1^KD on CD4⁺ T cell. Flow cytometry was employed to measure PD-L1 and CD4⁺ T cell proliferation levels. Western blot was utilized to detect related proteins.</div></div><div><h3>Results</h3><div>The expression of <em>LKB1</em> in BMMSCs derived from AML patients was decreased. Knockdown of <em>LKB1</em> in HS-5 resulted in upregulation of PD-L1 expression. Co-culture of peripheral blood CD4⁺ T cell with HS-5-LKB1^KD exhibited reduced CD4⁺ T cell proliferation compared to co-culture with HS-5-LKB1^con. Furthermore, blocking PD-L1 in the co-culture conditions could restore the reduced CD4⁺ T cell proliferation. Additionally, it was found that upregulation of the Wnt signaling pathway-related proteins following <em>LKB1</em> knockdown in HS-5, indicating that downregulating LKB1 could promote PD-L1 expression through activation of the Wnt signaling pathway.</div></div><div><h3>Conclusions</h3><div>The decreased expression of LKB1 in BMMSCs may activate the Wnt signaling pathway, leading to increased PD-L1 expression. This inhibited CD4⁺ T cell proliferation, which might lead to impaired anti-tumor immunity in AML patients and promote AML progression.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 6","pages":"Article 152856"},"PeriodicalIF":2.5,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142380713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pan-cancer analysis of ADAR1 with its prognostic relevance in low-grade glioma","authors":"Qin Yang ,&nbsp;Xin Li","doi":"10.1016/j.imbio.2024.152855","DOIUrl":"10.1016/j.imbio.2024.152855","url":null,"abstract":"<div><div>ADAR1, known as the primary enzyme for adenosine-to-inosine RNA editing, has recently been implicated in cancer development through both RNA editing-dependent and −independent pathways. These discoveries suggest that ADAR1′s functions may extend beyond our current understanding. A pan-cancer analysis offers a unique opportunity to identify both common and distinct mechanisms across various cancers, thereby advancing personalized medicine. Low-grade glioma (LGG), characterized by a diverse group of tumor cells, presents a challenge in risk stratification, leading to significant variations in treatment approaches. Recently discovered molecular alterations in LGG have helped to refine the stratification of of these tumors and offered novel targets for predicting likely outcomes. This study aims to provide a detailed analysis of ADAR mRNA across multiple cancers, emphasizing its prognostic significance in LGG. We observed inconsistent mRNA and consistent protein expression patterns of ADAR1/ADAR in pan-cancer analyses that across tumor types. ADAR mRNA expression did not always correlate with ADAR1 protein expression. Nevertheless, the transcript levels correlated significantly with genetic alterations, tumor mutation burden, microsatellite instability, overall survival, recurrence-free survival, immune marker presence, immune infiltration, and the survival of patients undergoing immunotherapy in select cancers. Furthermore, ADAR and its top 50 associated genes were primarily involved in mRNA-related events, as identified through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Utilizing the Cox proportional hazards model, we developed a 3-gene signature (ADAR, HNRNPK, and SMG7), which effectively stratified patients into high- and low-risk groups, with high-risk patients exhibiting poorer overall survival, higher tumor grades, and a greater number of non-codeletions. Overall, this signature was inversely related to immune infiltration across cancers. Transcription factor SPI1 and miR-206, potential upstream regulators of the signature genes, were closely linked to patient survival in LGG. The promoter regions of these genes were hypermethylated, further associating them with patient outcomes. Additionally, these genes displayed consistent drug susceptibility patterns. In conclusion, our findings reveal multiple aspects of ADAR1′s role in cancer and underscore its prognostic value in LGG, offering insights into potential therapeutic targets and strategies.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 6","pages":"Article 152855"},"PeriodicalIF":2.5,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of urine and serum IgG detection ELISA for tegumentary leishmaniasis diagnosis and prognosis","authors":"Raquel S.B. Câmara ,&nbsp;Isabela A.G. Pereira ,&nbsp;Daniela P. Lage ,&nbsp;Danniele L. Vale ,&nbsp;Fernanda Ludolf ,&nbsp;Nathália C. Galvani ,&nbsp;Camila S. Freitas ,&nbsp;João A. Oliveira-da-Silva ,&nbsp;Bárbara P.N. Assis ,&nbsp;Ana T. Chaves ,&nbsp;Mário S. Giusta ,&nbsp;Grasiele S.V. Tavares ,&nbsp;César N. Pereira ,&nbsp;Alexsandro S. Galdino ,&nbsp;Unaí Tupinambás ,&nbsp;Miguel A. Chávez-Fumagalli ,&nbsp;Vanessa P.M. Pascoal ,&nbsp;Marcela T.C. Eller ,&nbsp;Manoel O. da Costa Rocha ,&nbsp;Myron Christodoulides ,&nbsp;Eduardo A.F. Coelho","doi":"10.1016/j.imbio.2024.152853","DOIUrl":"10.1016/j.imbio.2024.152853","url":null,"abstract":"<div><p>Laboratorial diagnosis of tegumentary leishmaniasis (TL) is hampered by variable sensitivity and/or specificity of the tests, which are still hampered by blood́ invasive collection. In this context, in the present study, we develop a serum- and urine-based ELISA to TL diagnoses. A recombinant protein (rLiHyA), which was previously showed to be antigenic for the disease, as well as a B-cell epitope produced as synthetic peptide and a <em>Leishmania</em> antigenic extract (SLA), were used as antigens. A total of paired 205 urine and serum samples were used, which were comprised by samples from cutaneous (n = 30) and mucosal (n = 30) leishmaniasis patients, as well as from healthy individuals living in endemic region of disease (n = 45), of patients with Chagas disease (n = 30), leprosy (n = 35), malaria (n = 15) or HIV-infected (n = 20). Results showed that serum-based ELISA presented sensitivity of 24.0 %, 100 % and 41.0 %, when SLA, rLiHyA and synthetic peptide were used as antigens, and specificity of 98.4 %, 98.4 % and 98.4 %, respectively. The area under the curve (AUC) was calculated and results were 0.74, 1.0, and 0.71, respectively, when SLA, rLiHyA and synthetic peptide were used as antigens. Performing an urine-based ELISA, sensitivity was 28.0 %, 100 % and 75.0 %, respectively, when SLA, rLiHyA, and synthetic peptide were used, while specificity values were of 98.4 %, 98.4 % and 98.4 %, respectively. In addition, the AUC values were 0.82, 1.0, and 0.94, respectively. A significant drop in specific antibodies levels in both patientś serum and urine samples was found six months after treatment, suggesting a prognostic role of rLiHyA for TL. In conclusion, preliminary data suggest the potential of use patient urine to TL diagnoses.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 6","pages":"Article 152853"},"PeriodicalIF":2.5,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000718/pdfft?md5=c74d279d2152e029a1c8ed1b4745a0fc&pid=1-s2.0-S0171298524000718-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of CD24hiCD27+ regulatory B cells in human chronic rhinosinusitis with/without nasal polyps","authors":"Shiyu Tian ,&nbsp;Jiao Xia ,&nbsp;Ke Liu ,&nbsp;Youxiang Ma ,&nbsp;Hao Tian ,&nbsp;Weiwei Wang ,&nbsp;Ruxiang Zhang ,&nbsp;Chunli Zhao ,&nbsp;Shusheng Gong","doi":"10.1016/j.imbio.2024.152854","DOIUrl":"10.1016/j.imbio.2024.152854","url":null,"abstract":"<div><h3>Background</h3><div>Regulatory B cells (Bregs) reduce allergic and autoimmune inflammation. However, their role in chronic rhinosinusitis (CRS) remains unknown. This study investigated the frequency and function of Breg subsets in the peripheral blood of patients with CRS.</div></div><div><h3>Methods</h3><div>The demographic and clinical characteristics were compared among control, CRSsNP, neCRSwNP, and eCRSwNP groups. The expression of various Breg subtypes was evaluated in peripheral blood mononuclear cells (PBMCs) of patients with eosinophilic CRS with nasal polyps (eCRSwNP), non-eosinophilic CRS with nasal polyps (neCRSwNP), CRS without nasal polyps (CRSsNP). CD19⁺CD24^hiCD27⁺ B cells (B10 cells) were isolated by flow cytometry, followed by RNA sequencing (RNA-seq). Finally, IL-10 secreted by B10 cells were evaluated through the intracellular stain.</div></div><div><h3>Results</h3><div>A higher number of eosinophils in peripheral blood and nasal polyps were found in eCRSwNP compared with neCRSwNP, CRSsNP, and control groups. The frequency of B10 in the peripheral blood B cells (B10%) of patients with eCRSwNP was significantly lower than that in the neCRSwNP and control groups. B10% was negatively correlated with the quantity of tissue eosinophils, and the percentage and absolute value of peripheral blood eosinophils. The eCRSwNP, neCRSwNP and control groups had 1403 differentially expressed genes, 35 of which were identified in four highly enriched pathways. Additionally, the frequency of IL-10⁺B10 cells in peripheral blood was lower in patients with eCRSwNP than in the neCRSwNP and control groups.</div></div><div><h3>Conclusion</h3><div>This study is the first to reveal differences in both the quantity and IL-10 secretion of B10 cells in patients with eCRSwNP and neCRSwNP. These variations were strongly negatively associated with eosinophils in nasal polyps and peripheral blood. IL-10⁺B10 cells may play a key role in the pathological mechanisms of CRS, particularly the recurrence of eCRSwNP.</div></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 6","pages":"Article 152854"},"PeriodicalIF":2.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142328254","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction notice to “Increased levels of Th17 cells are associated with non-neuronal acetylcholine in COPD patients” [Immunobiology 219(5) (2014) 392–401]","authors":"","doi":"10.1016/j.imbio.2024.152806","DOIUrl":"10.1016/j.imbio.2024.152806","url":null,"abstract":"","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152806"},"PeriodicalIF":2.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S017129852400024X/pdfft?md5=32799ad5a8cec97d6f1991e1e20c7c50&pid=1-s2.0-S017129852400024X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A study on the efficacy and Safety Evaluation of a novel PD-1/CTLA-4 bispecific antibody","authors":"Qi Song ,&nbsp;Meiling Jiang ,&nbsp;Xinrong Pan ,&nbsp;Guanyue Zhou ,&nbsp;Xiaomeng Zhang","doi":"10.1016/j.imbio.2024.152844","DOIUrl":"10.1016/j.imbio.2024.152844","url":null,"abstract":"<div><p>Tumors constitute a significant health concern for humans, and PD-1 and CTLA-4 monoclonal antibodies have been proven effective in cancer treatment. Some researchers have identified that the combination of PD-1 and CTLA-4 dual blockade demonstrates superior therapeutic efficacy. However, the development of PD-1/CTLA-4 bispecific antibodies faces challenges in terms of both safety and efficacy. The present study discloses a novel PD-1/CTLA-4 bispecific antibody, designated as SH010. Experimental validation through surface plasmon resonance (SPR) confirmed that SH010 exhibits favorable binding activity with both PD-1 and CTLA-4. Flow cytometry analysis demonstrated stable binding of SH010 antibody to CHOK1 cells overexpressing human or cynomolgus monkey PD-1 protein and to 293F cells overexpressing human or cynomolgus monkey CTLA-4 protein. Moreover, it exhibited excellent blocking capabilities in protein binding between human PD-1 and PD-L1, as well as human CTLA-4 and CD80/CD86. Simultaneously, in <em>vitro</em> experiments indicate that SH010 exerts a significant activating effect on hPBMCs. In murine transplant models of human prostate cancer (22RV1) and small cell lung cancer (NCI-H69), administration of varying concentrations of the bispecific antibody significantly inhibits tumor growth. MSD analysis revealed that stimulation of hPBMCs from three different donors with SH010 did not induce the production of cytokine release syndrome. Furthermore, Single or repeated intravenous administrations of SH010 in cynomolgus monkeys show favorable systemic exposure without noticeable drug accumulation or apparent toxicity. In conclusion, SH010 represents a novel cancer therapeutic drug poised to enter clinical trials and obtain market approval.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 6","pages":"Article 152844"},"PeriodicalIF":2.5,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000627/pdfft?md5=f6449ebbf3632fd4a2aaa2465393d152&pid=1-s2.0-S0171298524000627-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Myeloperoxidase-deficient mice exposed to Zymosan exhibit severe neutrophilia and anemia with enhanced granulopoiesis and reduced erythropoiesis, accompanied by pulmonary inflammation","authors":"Misaki Yoshikawa ,&nbsp;Yuki Sato ,&nbsp;Mayu Sasaki ,&nbsp;Yasuaki Aratani","doi":"10.1016/j.imbio.2024.152843","DOIUrl":"10.1016/j.imbio.2024.152843","url":null,"abstract":"<div><p>We previously reported that myeloperoxidase-deficient (MPO^-/-) mice develop more severe neutrophil-rich lung inflammation than wild-type mice following intranasal Zymosan administration. Interestingly, we found that these mutant mice with severe lung inflammation also displayed pronounced neutrophilia and anemia, characterized by increased granulopoiesis and decreased erythropoiesis in the bone marrow, compared to wild-type mice. This condition was associated with higher concentrations of granulocyte-colony stimulating factor (G-CSF) in both the lungs and serum, a factor known to enhance granulopoiesis. Neutrophils accumulating in the lungs of MPO^-/- mice produced greater amounts of G-CSF than those in wild-type mice, indicating that they are a significant source of G-CSF. <em>In vitro</em> experiments using signal transduction inhibitors and Western blot analysis revealed that MPO^-/- neutrophils express higher levels of G-CSF mRNA in response to Zymosan, attributed to the upregulation of the IκB kinase/nuclear factor (NF)-κB pathway and the extracellular-signal-regulated kinase/NF-κB pathway. These findings highlight MPO as a critical regulator of granulopoiesis and erythropoiesis in inflamed tissues.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152843"},"PeriodicalIF":2.5,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000615/pdfft?md5=b9c73231ec42a6172f07292fd3134f99&pid=1-s2.0-S0171298524000615-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142058020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dexmedetomidine induces IL-10 secretion by B lymphocytes in the peripheral blood of patients with hepatocellular carcinoma","authors":"Miaomiao Qin ,&nbsp;Yining Chen ,&nbsp;Xinxin Wang ,&nbsp;Xiaobao Zhang ,&nbsp;Xiongxiong Pan","doi":"10.1016/j.imbio.2024.152842","DOIUrl":"10.1016/j.imbio.2024.152842","url":null,"abstract":"<div><h3>Background/aim</h3><p>To investigate the distribution of subpopulations of peripheral blood B lymphocytes in individuals with hepatocellular carcinoma (HCC), and to evaluate the effect of dexmedetomidine (DEX) on B lymphocyte differentiation in patients with HCC in vitro.</p></div><div><h3>Methods</h3><p>Peripheral blood mononuclear cells (PBMCs) were collected from the HCC group and the healthy group, and the distribution of peripheral blood B-lymphocyte subpopulations in the two groups was examined by Flow Cytometry (FCM). B lymphocytes extracted from the peripheral blood of the HCC group were divided into D0, D1, D2 and D4 groups according to the different dose of DEX in the culture medium (0 μM, 1 μM, 2 μM and 4 μM). After 72 h of in vitro culture, FCM was used to detect differences in the percentage of apoptotic B lymphocytes and the percentage of B lymphocytes that can express interleukin 10(IL-10) and transforming growth factor-β (TGF-β) in each group.</p></div><div><h3>Results</h3><p>In contrast to the healthy group, the HCC group exhibited a statistically significant increase in the proportion of CD19 + CD73 + B lymphocyte subpopulation (P&lt;0.05). In the in vitro culture experiment, the differences in apoptosis of B lymphocytes and the percentage of TGF-β expression in each group were not statistically significant; When compared to the control group, there was a significant increase in the percentage of B lymphocytes expressing IL-10 across the D1, D2, and D4 groups (P&lt;0.05).</p></div><div><h3>Conclusion</h3><p>The peripheral blood of HCC patients is characterized by an elevated presence of CD19 + CD73 + B lymphocyte subpopulations; DEX may have an immunosuppressive effect by promoting IL-10 secretion from peripheral blood B lymphocytes of HCC patients.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152842"},"PeriodicalIF":2.5,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000603/pdfft?md5=9c402ab73f9d18329b994075cdbc52a7&pid=1-s2.0-S0171298524000603-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141998070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR4/TNFR1 blockade suppresses STAT1/STAT3 expression and increases SOCS3 expression in modulation of LPS-induced macrophage responses","authors":"Ritasha Sawoo,&nbsp;Biswadev Bishayi","doi":"10.1016/j.imbio.2024.152840","DOIUrl":"10.1016/j.imbio.2024.152840","url":null,"abstract":"<div><p>Due to the urgent need to create appropriate treatment techniques, which are currently unavailable, LPS-induced sepsis has become a serious concern on a global scale. The primary active component in the pathophysiology of inflammatory diseases such as sepsis is the Gram-negative bacterial lipopolysaccharide (LPS). LPS interacts with cell surface TLR4 in macrophages, causing the formation of reactive oxygen species (ROS), TNF-α, IL-1β and oxidative stress. It also significantly activates the MAPKs and NF-κB pathway. Excessive production of pro-inflammatory cytokines is one of the primary characteristic features in the onset and progression of inflammation. Cytokines mainly signal through the JAK/STAT pathway. We hypothesize that blocking of TLR4 along with TNFR1 might be beneficial in suppressing the effects of STAT1/STAT3 due to the stimulation of SOCS3 proteins. Prior to the LPS challenge, the macrophages were treated with antibodies against TLR4 and TNFR1 either individually or in combination. On analysis of the macrophage populations by flowcytometry, it was seen that receptor blockade facilitated the phenotypic shift of the M1 macrophages towards M2 resulting in lowered oxidative stress. Blocking of TLR4/TNFR1 upregulated the SOCS3 and mTOR expressions that enabled the transition of inflammatory M1 macrophages towards the anti-inflammatory M2 phenotype, which might be crucial in curbing the inflammatory responses. Also the reduction in the production of inflammatory cytokines such as IL-6, IL-1β due to the reduction in the activation of the STAT1 and STAT3 molecules was observed in our combination treatment group. All these results indicated that neutralization of both TLR4 and TNFR1 might provide new insights in establishing an alternative therapeutic strategy for LPS-sepsis.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152840"},"PeriodicalIF":2.5,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000585/pdfft?md5=6fa21168b1f9f1a7014808462aaf447f&pid=1-s2.0-S0171298524000585-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141912445","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated machine learning screened glutamine metabolism-associated biomarker SLC1A5 to predict immunotherapy response in hepatocellular carcinoma","authors":"Guixiong Zhang ,&nbsp;Yitai Xiao ,&nbsp;Hang Liu ,&nbsp;Yanqin Wu ,&nbsp;Miao Xue ,&nbsp;Jiaping Li","doi":"10.1016/j.imbio.2024.152841","DOIUrl":"10.1016/j.imbio.2024.152841","url":null,"abstract":"<div><p>Hepatocellular carcinoma (HCC) stands as one of the most prevalent malignancies. While PD-1 immune checkpoint inhibitors have demonstrated promising therapeutic efficacy in HCC, not all patients exhibit a favorable response to these treatments. Glutamine is a crucial immune cell regulatory factor, and tumor cells exhibit glutamine dependence. In this study, HCC patients were divided into two subtypes (C1 and C2) based on glutamine metabolism-related genes via consensus clustering. The C1 pattern, in contrast to C2, was associated with a lower survival probability among HCC patients. Additionally, the C1 pattern exhibited higher proportions of patients with advanced tumor stages. The activity of C1 in glutamine metabolism and transport is significantly enhanced, while its oxidative phosphorylation activity is reduced. And, C1 was mainly involved in the progression-related pathway of HCC. Furthermore, C1 exhibited high levels of immunosuppressive cells, cytokine-receptor interactions and immune checkpoint genes, suggesting C1 as an immunosuppressive subtype. After stepwise selection based on integrated four machine learning methods, SLC1A5 was finally identified as the pivotal gene that distinguishes the subtypes. The expression of SLC1A5 was significantly positively correlated with immunosuppressive status. SLC1A5 showed the most significant correlation with macrophage infiltration, and this correlation was confirmed through the RNA-seq data of CLCA project and our cohort. Low-SLC1A5-expression samples had better immunogenicity and responsiveness to immunotherapy. As expected, SubMap and survival analysis indicated that individuals with low SLC1A5 expression were more responsive to anti-PD1 therapy. Collectively, this study categorized HCC patients based on glutamine metabolism-related genes and proposed two subclasses with different clinical traits, biological behavior, and immune status. Machine learning was utilized to identify the hub gene SLC1A5 for HCC classification, which also could predict immunotherapy response.</p></div>","PeriodicalId":13270,"journal":{"name":"Immunobiology","volume":"229 5","pages":"Article 152841"},"PeriodicalIF":2.5,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0171298524000597/pdfft?md5=9b728266aff2bc1d2b2340dc90eeaa7f&pid=1-s2.0-S0171298524000597-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141884016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}