Immune regulation of the gut-brain axis and lung-brain axis involved in ischemic stroke

Local ischemia often causes a series of inflammatory reactions when both brain immune cells and the peripheral immune response are activated.In the human body,the gut and lung are regarded as the key reactional targets that are initiated by brain ischemic attacks.Mucosal microorganisms play an important role in immune regulation and metabolism and affect blood-brain barrier permeability.In addition to the relationship between peripheral organs and central areas and the intestine and lung also interact among each other.Here,we review the molecular and cellular immune mechanisms involved in the pathways of inflammation across the gut-brain axis and lung-brain axis.We found that abnormal intestinal flora,the intestinal microenvironment,lung infection,chronic diseases,and mechanical ventilation can worsen the outcome of ischemic stroke.This review also introduces the influence of the brain on the gut and lungs after stroke,highlighting the bidirectional feedback effect among the gut,lungs,and brain.

Interplay between mesenchymal stromal cells and the immune system after transplantation: implications for advanced cell therapy in the retina

Advanced mesenchymal stromal cell-based therapies for neurodegenerative diseases are widely investigated in preclinical models.Mesenchymal stromal cells are well positioned as therapeutics because they address the underlying mechanisms of neurodegeneration,namely trophic factor deprivation and neuroinflammation.Most studies have focused on the beneficial effects of mesenchymal stromal cell transplantation on neuronal survival or functional improvement.However,little attention has been paid to the interaction between mesenchymal stromal cells and the host immune system due to the immunomodulatory properties of mesenchymal stromal cells and the long-held belief of the immunoprivileged status of the central nervous system.Here,we review the crosstalk between mesenchymal stromal cells and the immune system in general and in the context of the central nervous system,focusing on recent work in the retina and the importance of the type of transplantation.

DNA damage response-related immune activation signature predicts the response to immune checkpoint inhibitors: from gastrointestinal cancer analysis to pan-cancer validation

Objective: DNA damage response(DDR) deficiency has emerged as a prominent determinant of tumor immunogenicity. This study aimed to construct a DDR-related immune activation(DRIA) signature and evaluate the predictive accuracy of the DRIA signature for response to immune checkpoint inhibitor(ICI) therapy in gastrointestinal(GI) cancer.Methods: A DRIA signature was established based on two previously reported DNA damage immune response assays. Clinical and gene expression data from two published GI cancer cohorts were used to assess and validate the association between the DRIA score and response to ICI therapy. The predictive accuracy of the DRIA score was validated based on one ICI-treated melanoma and three pan-cancer published cohorts.Results: The DRIA signature includes three genes(CXCL10, IDO1, and IFI44L). In the discovery cancer cohort, DRIA-high patients with gastric cancer achieved a higher response rate to ICI therapy than DRIA-low patients(81.8% vs. 8.8%;P < 0.001), and the predictive accuracy of the DRIA score [area under the receiver operating characteristic curve(AUC) = 0.845] was superior to the predictive accuracy of PD-L1 expression, tumor mutational burden, microsatellite instability, and Epstein–Barr virus status. The validation cohort demonstrated that the DRIA score identified responders with microsatellite-stable colorectal and pancreatic adenocarcinoma who received dual PD-1 and CTLA-4 blockade with radiation therapy. Furthermore, the predictive performance of the DRIA score was shown to be robust through an extended validation in melanoma, urothelial cancer, and pan-cancer.Conclusions: The DRIA signature has superior and robust predictive accuracy for the efficacy of ICI therapy in GI cancer and pancancer, indicating that the DRIA signature may serve as a powerful biomarker for guiding ICI therapy decisions.

Immune checkpoint inhibitor-associated gastritis:Patterns and management

Immune checkpoint inhibitors(ICIs)are widely used due to their effectiveness in treating various tumors.Immune-related adverse events(irAEs)are defined as adverse effects resulting from ICI treatment.Gastrointestinal irAEs are a common type of irAEs characterized by intestinal side effects,such as diarrhea and colitis,which may lead to the cessation of ICIs.Although irAE gastritis is rarely reported,it may lead to serious complications such as gastrorrhagia.Furthermore,irAE gastritis is often difficult to identify early due to its diverse symptoms.Although steroid hormones and immunosuppressants are commonly used to reverse irAEs,the best regimen and dosage for irAE gastritis remains uncertain.In addition,the risk of recurrence of irAE gastritis after the reuse of ICIs should be considered.In this editorial,strategies such as early identification,pathological diagnosis,mana-gement interventions,and immunotherapy rechallenge are discussed to enable clinicians to better manage irAE gastritis and improve the prognosis of these patients.

Immune consequences of exercise in hypoxia:A narrative review

Immune outcomes are key mediators of many health benefits of exercise and are determined by exercise type,dose(frequency/duration,intensity),and individual characteristics.Similarly,reduced availability of ambient oxygen(hypoxia)modulates immune functions depending on the hypoxic dose and the individual capacity to respond to hypoxia.How combined exercise and hypoxia(e.g.,high-altitude training)sculpts immune responses is not well understood,although such combinations are becoming increasingly popular.Therefore,in this paper,we summarize the impact on immune responses of exercise and of hypoxia,both independently and together,with a focus on specialized cells in the innate and adaptive immune system.We review the regulation of the immune system by tissue oxygen levels and the overlapping and distinct immune responses related to exercise and hypoxia,then we discuss how they may be modulated by nutritional strategies.Mitochondrial,antioxidant,and anti-inflammatory mechanisms underlie many of the adaptations that can lead to improved cellular metabolism,resilience,and overall immune functions by regulating the survival,differentiation,activation,and migration of immune cells.This review shows that exercise and hypoxia can impair or complement/synergize with each other while regulating immune system functions.Appropriate acclimatization,training,and nutritional strategies can be used to avoid risks and tap into the synergistic potentials of the poorly studied immune consequences of exercising in a hypoxic state.

The early life immune dynamics and cellular drivers at single-cell resolution in lamb forestomachs and abomasum

Background Four-chambered stomach including the forestomachs(rumen,reticulum,and omasum)and abomasum allows ruminants convert plant fiber into high-quality animal products.The early development of this four-chambered stomach is crucial for the health and well-being of young ruminants,especially the immune development.However,the dynamics of immune development are poorly understood.Results We investigated the early gene expression patterns across the four-chambered stomach in Hu sheep,at 5,10,15,and 25 days of age.We found that forestomachs share similar gene expression patterns,all four stomachs underwent widespread activation of both innate and adaptive immune responses from d 5 to 25,whereas the metabolic function were significantly downregulated with age.We constructed a cell landscape of the four-chambered stomach using single-cell sequencing.Integrating transcriptomic and single-cell transcriptomic analyses revealed that the immune-associated module hub genes were highly expressed in T cells,monocytes and macrophages,as well as the defense-associated module hub genes were highly expressed in endothelial cells in the four-stomach tissues.Moreover,the non-immune cells such as epithelial cells play key roles in immune maturation.Cell communication analysis predicted that in addition to immune cells,non-immune cells recruit immune cells through macrophage migration inhibitory factor signaling in the forestomachs.Conclusions Our results demonstrate that the immune and defense responses of four stomachs are quickly developing with age in lamb's early life.We also identified the gene expression patterns and functional cells associated with immune development.Additionally,we identified some key receptors and signaling involved in immune regulation.These results help to understand the early life immune development at single-cell resolution,which has implications to develop nutritional manipulation and health management strategies based on specific targets including key receptors and signaling pathways.

A Prognostic Biomarker for Bladder Cancer Correlated with Immune Infiltration Is PAEP

Background: A major cause of cancer death worldwide is bladder cancer, which is the most common malignant tumor of the urinary tract. PAEP is a member of the kernel lipocalin superfamily whose members share relatively low sequence similarity but have highly conserved exon/intron structure and three-dimensional protein folding. Most lipocalins are clustered on the long arm of chromosome 9. The purpose of this study was to clarify the correlation between PAEP expression level and bladder cancer. Methods: In the TCGA database, we obtained clinical and RNA sequencing data of 431 BLCA patients, including 412 BLCA tissues and 19 normal bladder tissues in the study. Analyses of bioinformatics were conducted in this study to determine the role of PAEP in bladder cancer. A quantitative real-time PCR method was used to quantitate the gene expression profile. Additionally, the effect of PAEP on tumor immune infiltration and prognosis was analyzed. Results: PAEP was a poor prognostic biomarker of bladder cancer because it was significantly upregulated. bladder cancer patients with higher PAEP expression had poor outcomes. An AUC of 0.780 was calculated from the area under the ROC curve. PAEP was associated with T stage, pathologic stage, Histologic grade and Subtype of bladder cancer patients, and served as an independent predictor of overall survival in bladder cancer patients. Functional enrichment analysis revealed PAEP was obviously enriched in pathways connected with carcinogenesis and immunosuppression. The expression of PAEP was significantly associated with tumor immune cells and immune checkpoints according to ssGSEA and Spearman correlation analysis. Conclusions: In this study, we screened and detected a mRNA, PAEP is a prognostic and immune-related biomarker in BLCA, which may contribute to the early diagnosis and treatment of BLCA.

Hepatocellular carcinoma immune microenvironment and check point inhibitors-current status

Hepatocellular carcinoma(HCC)is the most common primary tumor of the liver and has a high mortality rate.The Barcelona Clinic Liver Cancer staging system in addition to tumor staging also links the modality of treatment available to a particular stage.The recent description of the tumor microenvironment(TME)in HCC has provided a new concept of immunogenicity within the HCC.Virusrelated HCC has been shown to be more immunogenic with higher expression of cytotoxic T lymphocytes and decreased elements for immunosuppression such as regulatory T cells.This immunogenic milieu provides a better response to immunotherapy especially immune checkpoint inhibitors(ICIs).In addition,the recent data on combining locoregional therapies and other strategies may convert the less immunogenic state of the TME towards higher immunogenicity.Therefore,data are emerging on the use of combinations of locoregional therapy and ICIs in unresectable or advanced HCC and has shown better survival outcomes in this difficult population.

Human herpesvirus 7 meningitis in an adolescent with normal immune function:A case report

BACKGROUND Human herpesvirus type 7(HHV-7)is a less common herpes virus that usually causes mild,self-limiting illnesses.However,in recent years,there have been increasing reports of HHV-7 causing serious central nervous system infections,especially meningitis.The pathogenesis and clinical features of HHV-7 meningitis,particularly in adolescents with normal immune function,remain incompletely studied.Therefore,the purpose of this report is to share a case of HHV-7 meningitis in an immunocompetent adolescent with a view to deepening our understanding of the disease.CASE SUMMARY A 12-year-old female was admitted with fever,headache,and vomiting.4 d before admission,the patient developed a fever without obvious induction,with a temperature up to 39.5℃,no convulsions,accompanied by chills,headaches,fatigue,and no muscle aches.The patient was treated with fever reduction,which could be reduced to 38℃;repeated high fever,accompanied by vomiting 7-8 times;and no abdominal pain or diarrhea.The patient was diagnosed with"acute suppurative tonsillitis"in a local hospital,and the blood routine was generally normal.The patient was given symptomatic support treatment such as"ceftriaxone sodium"and antiemetic rehydration for 2 d,and his condition did not improve.The patient's physical examination showed pharyngeal congestion,bilateral tonsil grade I hypertrophy,regression of purulent secretions,and cervical resistance.Ocular B-ultrasound:Opacity of the vitreous body and edema of the optic disc in both eyes.Optical coherence tomography examination showed that the macular fovea was generally normal in both eyes,with edema of the optic disc.DNA virus monitoring results:HHV-7.We gave ganciclovir antiviral therapy,dexamethasone anti-inflammatory treatment,mannitol to reduce cranial pressure,omeprazole to protect gastrointestinal mucosa,and calcium and potassium supplementation.CONCLUSION This study reports a case of HHV-7 meningitis in an adolescent with normal immune function.Through comprehensive analysis of the clinical manifestations,laboratory tests,and treatment methods of the patient,it is found that early identification and antiviral treatment are essential for the outcome of the disease.This case suggests that despite normal immune function,adolescents may still suffer from herpes virus type 7 meningitis,so clinicians should be vigilant and take effective treatment measures in time.

To explore the mechanism of Yigong San anti-gastric cancer and immune regulation

BACKGROUND Yigong San(YGS)is a representative prescription for the treatment of digestive disorders,which has been used in clinic for more than 1000 years.However,the mechanism of its anti-gastric cancer and regulate immunity are still remains unclear.AIM To explore the mechanism of YGS anti-gastric cancer and immune regulation.METHODS Firstly,collect the active ingredients and targets of YGS,and the differentially expressed genes of gastric cancer.Secondly,constructed a protein-protein interaction network between the targets of drugs and diseases,and screened hub genes.Then the clinical relevance,mutation and repair,tumor microenvironment and drug sensitivity of the hub gene were analyzed.Finally,molecular docking was used to verify the binding ability of YGS active ingredient and hub genes.RESULTS Firstly,obtained 55 common targets of gastric cancer and YGS.The Kyoto Encyclopedia of Genes and Genomes screened the microtubule-associated protein kinase signaling axis as the key pathway and IL6,EGFR,MMP2,MMP9 and TGFB1 as the hub genes.The 5 hub genes were involved in gastric carcinogenesis,staging,typing and prognosis,and their mutations promote gastric cancer progression.Finally,molecular docking results confirmed that the components of YGS can effectively bind to therapeutic targets.CONCLUSION YGS has the effect of anti-gastric cancer and immune regulation.

A mite parasitoid,Pyemotes zhonghuajia,negatively impacts the fitness traits and immune response of the fall armyworm,Spodoptera frugiperda

Parasitoids are key regulators in ecological communities and widely used as agents in biocontrol programmes.The fall armyworm,Spodoptera frugiperda,recently invaded multiple continents and caused substantial economic losses in agriculture.Pyemotes zhonghuajia,a newly identified mite parasitoid,has shown potential for controlling various agricultural insect pests.Therefore,this study tested the performance of P.zhonghuajia in parasitising S.frugiperda.We also investigated the sublethal effects of parasitism by P.zhonghuajia on host fitness traits,transgenerational impacts,and cellular and humoral immunity.Our result showed that the fifth-instar larvae of S.frugiperda parasitised by 40 P.zhonghuajia were all dead(i.e.,a lethal effect),while parasitism by 5 or 10 P.zhonghuajia was considered sublethal since many S.frugiperda survived to adulthood and produced offspring after mating.The sublethal influences from parasitism by P.zhonghuajia resulted in reduced pupal weight,adult emergence rate and fecundity,but increased developmental time and longevity.Parasitism at both lethal(40 mites)and sublethal(10 mites)levels impaired the cellular and humoral immunity of S.frugiperda.This study presents the first empirical evidence that mite parasitoids can negatively influence host immunity.Moreover,it provides insights into the biocontrol potential of mite parasitoids and their interactions with hosts.

Immune checkpoint inhibition mediated with liposomal nanomedicine for cancer therapy

Immune checkpoint blockade(ICB)therapy for cancer has achieved great success both in clinical results and on the market.At the same time,success drives more attention from scientists to improve it.However,only a small portion of patients are responsive to this therapy,and it comes with a unique spectrum of side effects termed immunerelated adverse events(irAEs).The use of nanotechnology could improve ICBs’delivery to the tumor,assist them in penetrating deeper into tumor tissues and alleviate their irAEs.Liposomal nanomedicine has been investigated and used for decades,and is well-recognized as the most successful nano-drug delivery system.The successful combination of ICB with liposomal nanomedicine could help improve the efficacy of ICB therapy.In this review,we highlighted recent studies using liposomal nanomedicine(including new emerging exosomes and their inspired nanovesicles)in associating ICB therapy.

PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable prognosis.The dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment failure.The elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also underestimated.Here,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of HCC.Then,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT assays.Our findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer prognosis.The methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver tissues.Besides,noteworthy associations were observed between PHLDA2 expression and immune infiltration in HCC.In addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in HCC.In vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy drugs.Meanwhile,we found that TGF-βinduced the expression of PHLDA2 in vitro.The GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling pathway.Our study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

Major royal-jelly proteins intake modulates immune functions and gut microbiota in mice

In this study,we investigated the effects of major royal jelly proteins(MRJPs)on the estrogen,gut microbiota,and immunological responses in mice.Mice given 250 or 500 mg/kg,not 125 mg/kg of MRJPs,enhanced the proliferation of splenocytes in response to mitogens.The splenocytes and mesenteric lymphocytes activated by T-cell mitogens(Con A and anti-CD3/CD28 antibodies)released high levels of IL-2 but low levels of IFN-γand IL-17A.The release of IL-4 was unaffected by MRJPs.Additionally,splenocytes and mesenteric lymphocytes activated by LPS were prevented by MRJPs at the same dose as that required for producing IL-1βand IL-6,two pro-inflammatory cytokines.The production of IL-1β,IL-6,and IFN-γwas negatively associated with estrogen levels,which were higher in the MRJP-treated animals than in the control group.Analysis of the gut microbiota revealed that feeding mice 250 mg/kg of MRJPs maintained the stability of the natural intestinal microflora of mice.Additionally,the LEf Se analysis identified biomarkers in the MRJP-treated mice,including Prevotella,Bacillales,Enterobacteriales,Gammaproteobacteria,Candidatus_Arthromitus,and Shigella.Our results showed that MRJPs are important components of royal jelly that modulate host immunity and hormone levels and help maintain gut microbiota stability.

Immunological disturbance effect of exogenous histamine towards key immune cells

Histamine in food has attracted widespread attention due to the potential toxicity and associated health risk.However,its influences on immunological components,especially the function of key immune cells,are still poorly known.In this work,we explored the effects of exogenous histamine on the function of key immune cells such as intestinal epithelial cells,dendritic cells,and T cells.The results showed that histamine could affect the expression of allergy-related genes in CMT93 cells at a high dose of histamine.Moreover,it’s found that histamine could cause an imbalance in the levels of relevant immune factors secreted by dendritic cells and T cells,especially those related to allergy.At the same time,the proportion of MHC class IIpositive dendritic cells and the proportion of T helper 2(Th2)cells in CD4^(+)T cells increased after histamine stimulation.We concluded that the presence of a certain level of histamine in food may affect the expression of allergy-related cytokines,disrupt the balance of the immune homeostasis,and potentially lead to adverse immune reactions.This work demonstrated the importance of including the estimation of histamine’s immune safety in aquatic products rather than merely considering the potential risk of food poisoning.

Gustave Roussy Immune Score——结直肠癌患者的新型预后评分

目的探讨Gustave Roussy Immune Score(GRIm评分)在结直肠癌(CRC)根治术后患者预后评估中的价值。方法本研究共纳入2004年6月至2019年8月271例CRC根治术后患者。分析GRIm评分与CRC临床病理特征的关系。采用Kaplan-Meier法绘制CRC患者无病生存时间(DFS)曲线,生存差异行Log-rank检验;Cox风险比例回归模型分析影响CRC患者预后的因素;校准曲线和受试者工作特征(ROC)曲线检验基于GRIm评分的列线图的预测效能。结果GRIm评分与性别、肿瘤部位、神经侵犯、N分期、美国癌症联合委员会(AJCC)分期、白蛋白(ALB)评分和乳酸脱氢酶(LDH)评分有关(P<0.05);GRIm简化评分与肿瘤部位、肿瘤直径、癌栓、ALB评分和LDH评分有关(P<0.05)。Cox风险比例回归模型显示,GRIm评分是影响CRC患者DFS的独立因素(HR=2.546,95%CI:1.644~3.943,P<0.05)。包括GRIm评分的列线图对CRC患者DFS的预测能力优于第8版AJCC分期系统。结论GRIm评分是影响CRC患者DFS的独立因素,基于GRIm评分的列线图可以帮助临床医师有效评估CRC患者的预后,制定个体化治疗方案。

Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.

IQGAP3 promotes the progression of glioma as an immune and prognostic marker

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

Transcriptome analysis reveals immune-related genes in tissues of Vibrio anguillarum-infected turbot Scophthalmus maximus

Turbot Scophthalmus maximus is an important mariculture fish species with high economic value.However,the bacterial diseases caused by Vibrio anguillarum infection bring huge economic losses to the turbot aquaculture industry.To understand the immune response of the turbot against V.anguillarum infection and to explore novel immune-related genes,the transcriptome analysis of turbot spleen and gills were conducted after V.anguillarum infection.Differentially expressed genes(DEGs)were identified in spleen and gill of the turbot amounted to 17261 and 16436,respectively.A large number of immunerelated DEGs were enriched in cytokine-cytokine receptor interaction signaling pathway,and the others by the kyoto encyclopedia of genes and genomes(KEGG)enrichment.The gene ontology(GO)classification analysis revealed that V.anguillarum infection had the greatest effect on biological processes and cellular components.Twelve immune-related DEGs were identified in the spleen(cstl.1,egfl6,lamb21,v2rx4,calcr,and gpr78a)and gills(ghra,sh3gl2a,cst12,inhbaa,cxcl8,and il-1b)by heat map.The proteinprotein interaction(PPI)networks were constructed to analyze the immune mechanism.The results demonstrate that the maturation and antigen processing of major histocompatibility complex(MHC)class II molecule,and calcitonin-or adrenomedullin-regulated physiological activity were important events in the immunity of turbot against V.anguillarum infection.In the gills,the protein interactions in TGF-βsignaling pathway,production of inflammatory factors,and endocytosis regulation were most significant.Our research laid a foundation for discovering novel immune-related genes and enriching the knowledge of immune mechanisms of turbot against V.anguillarum infection.

CRABP2 regulates infiltration of cancer-associated fibroblasts and immune response in melanoma

Finding biomarkers for immunotherapy is an urgent issue in cancer treatment.Cellular retinoic acid-binding protein 2(CRABP2)is a controversial factor in the occurrence and development of human tumors.However,there is limited research on the relationship between CRABP2 and immunotherapy response.This study found that negative correlations of CRABP2 and immune checkpoint markers(PD-1,PD-L1,and CTLA-4)were observed in breast invasive carcinoma(BRCA),skin cutaneous melanoma(SKCM),stomach adenocarcinoma(STAD)and testicular germ cell tumors(TGCT).In particular,in SKCM patients who were treated with PD-1 inhibitors,high levels of CRABP2 predicted poor prognosis.Additionally,CRABP2 expression was elevated in cancer-associated fibroblasts(CAFs)at the single-cell level.The expression of CRABP2 was positively correlated with markers of CAFs,such as MFAP5,PDPN,ITGA11,PDGFRα/βand THY1 in SKCM.To validate the tumor-promoting effect of CRABP2 in vivo,SKCM xenograft mice models with CRABP2 overexpression have been constructed.These models showed an increase in tumor weight and volume.Enrichment analysis indicated that CRABP2 may be involved in immunerelated pathways of SKCM,such as extracellular matrix(ECM)receptor interaction and epithelial-mesenchymal transition(EMT).The study suggests that CRABP2 may regulate immunotherapy in SKCM patients by influencing infiltration of CAFs.In conclusion,this study provides new insights into the role of CRABP2 in immunotherapy response.The findings suggest that CRABP2 may be a promising biomarker for PD-1 inhibitors in SKCM patients.Further research is needed to confirm these findings and to explore the clinical implications of CRABP2 in immunotherapy.