Exploring the modulatory role of bovine lactoferrin on the microbiome and the immune response in healthy and Shiga toxin‑producing E.coli challenged weaned piglets

Background Post-weaned piglets suffer from F18+Escherichia coli(E.coli)infections resulting in post-weaning diar-rhoea or oedema disease.Frequently used management strategies,including colistin and zinc oxide,have contrib-uted to the emergence and spread of antimicrobial resistance.Novel antimicrobials capable of directly interacting with pathogens and modulating the host immune responses are being investigated.Lactoferrin has shown promising results against porcine enterotoxigenic E.coli strains,both in vitro and in vivo.Results We investigated the influence of bovine lactoferrin(bLF)on the microbiome of healthy and infected weaned piglets.Additionally,we assessed whether bLF influenced the immune responses upon Shiga toxin-producing E.coli(STEC)infection.Therefore,2 in vivo trials were conducted:a microbiome trial and a challenge infection trial,using an F18+STEC strain.BLF did not affect theα-andβ-diversity.However,bLF groups showed a higher relative abundance(RA)for the Actinobacteria phylum and the Bifidobacterium genus in the ileal mucosa.When analysing the immune response upon infection,the STEC group exhibited a significant increase in F18-specific IgG serum levels,whereas this response was absent in the bLF group.Conclusion Taken together,the oral administration of bLF did not have a notable impact on theα-andβ-diversity of the gut microbiome in weaned piglets.Nevertheless,it did increase the RA of the Actinobacteria phylum and Bifi-dobacterium genus,which have previously been shown to play an important role in maintaining gut homeostasis.Furthermore,bLF administration during STEC infection resulted in the absence of F18-specific serum IgG responses.

Enteral nutrition and immune modulation of acute pancreatitis

Enteral nutrition has been strongly recommended by major scientific societies for the nutritional management of patients with acute pancreatitis.Providing severe acute pancreatitis patients with enteral nutrition within the first 24-48 h of hospital admission can help improve outcomes compared to parenteral nutrition and no feeding.New research is focusing in on when and what to feed to best improve outcomes for acute pancreatitis patients.Early enteral nutrition have the potential to modulate the immune responses.Despite this consistent evidence of early enteral nutrition in patients with acute pancreatitis,clinical practice continues to vary due to individual clinician preference.Achieving the immune modulating effects of enteral nutrition heavily depend on proper placement of the feeding tube and managing any tube feeding associated complications.The current article reviews the immune modulating effects of enteral nutrition and pro-and prebiotics and suggests some practical tools that help improve the patient adherence and tolerance to the tube feeding.Proper selection of the type of the tube,close monitoring of the tube for its placement,patency and securing its proper placement and routine checking the gastric residual volume could all help improve the outcome.Using peptide-based and high medium chaintriglycerides feeding formulas help improving feeding tolerance.

Influences of immersion bathing in Bacillus velezensis DY-6 on growth performance,non-specific immune enzyme activities and gut microbiota of Apostichopus japonicus

In this study, the influences of immersion bathing in different concentrations of Bacillus velezensis DY-6 on the body weight gain rate and non-specific immune enzyme activities of the coelom fluid of sea cucumber (Apostichopus japonicus) were determined in order to obtain the optimum bacterial concentration. The gut microbiota change in A. japonicus was then analyzed through high-throughput sequencing during the immersion bathing in B. velezensis DY-6 at the optimum concentration for 49 d. The results illustrate that the body weight growth rate of all bathing groups was higher than that of the control. The highest growth rate (25.3%) was achieved when the bacterial concentration was 1×10^3 CFU/mL. The activities of non-specific immune enzymes (ACP, AKP, SOD and LZM) of all bathing groups increased, and the activities of the enzymes of groups bathed with the bacterium at 1×10^3 and 1×10^4 CFU/mL reached the highest on day 21 and day 28. Taking the growth rate and economic cost into consideration, the optimum concentration of B. velezensis DY-6 was 1×10^3 CFU/mL. The influences of immersion bathing in B. velezensis DY-6 at 1×10^3 CFU/mL on the gut microbiota of A. japonicus were then evaluated through 16S rDNA sequencing analysis. Results showed that the gut microbiota changed with the addition of B. velezensis DY-6, and the richness and diversity of the gut microbiota peaked twice on day 14 and day 21, respectively. In association with the non-specific immune enzyme activities and if day 28 was selected as the dividing point, the community structure of the gut microbiota could be obviously divided into two types. The correlation analysis revealed that the non-specific immune enzyme activities were correlated significantly to some gut bacteria (in the phyla Firmicutes, Proteobacteria, and Bacteroidetes) after immersion bathing in B. velezensis DY-6. Our findings will provide the theoretical foundation for probiotic application in sea cucumber farming.

IMMUNE RBF NETWORK AND ITS APPLICATION IN THE MODULATION-STYLE RECOGNITION OF RADAR SIGNALS

Based on Immune Programming(IP), a novel Radial Basis Function (RBF) networkdesigning method is proposed. Through extracting the preliminary knowledge about the widthof the basis function as the vaccine to form the immune operator, the algorithm reduces thesearching space of canonical algorithm and improves the convergence speed. The application ofthe RBF network trained with the algorithm in the modulation-style recognition of radar signalsdemonstrates that the network has a fast convergence speed with good performances.

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

Shortage of appropriate donor grafts is the foremost current problem in organ transplantation. As a logical consequence, waiting times have extended and pretransplant mortality rates were significantly increasing. The implementation of a priority-based liver allocation system using the model of end-stage liverdisease(MELD) score helped to reduce waiting list mortality in liver transplantation(LT). However, due to an escalating organ scarcity, pre-LT MELD scores have significantly increased and liver recipients became more complex in recent years. This has finally led to posttransplant decreasing survival rates, attributed mainly to elevated rates of infectious and immunologic complications. To meet this challenging development, an increasing number of extended criteria donor grafts are currently accepted, which may, however, aggravate the patients' infectious and immunologic risk profiles. The administration of intravenous immunoglobulins(IVIg) is an established treatment in patients with immune deficiencies and other antibody-mediated diseases. In addition, IVIg was shown to be useful in treatment of several disorders caused by deterioration of the cellular immune system. It proved to be effective in preventing hyperacute rejection in highly sensitized kidney and heart transplants. In the liver transplant setting, the administration of specific Ig against hepatitis B virus is current standard in post-LT antiviral prophylaxis. The mechanisms of action of IVIg are complex and not fully understood. However, there is increasing experimental and clinical evidence that IVIg has an immuno-balancing impact by a combination of immuno-supporting and immuno-suppressive properties. It may be suggested that, especially in the context of a worsening organ shortage with all resulting clinical implications, liver transplant patients should benefit from immuno-regulatory capabilities of IVIg. In this review, perspectives of immune modulation by IVIg and impact on outcome in liver transplant patients are described.

Non-specific immune response of bullfrog Rana catesbeiana to intraperitoneal injection of bacterium Aeromonas hydrophila

Non-specific immune response of bullfrog Rana catesbeiana to pathogenic Aeromonas hydrophila was studied to 60 individuals in two groups.Each bullfrog in bacterium-injected group was injected intraperitoneally(i.p.) with 0.2 ml bacterial suspension at a density of 5.2 × 106 CFU/ml,while each one in control group injected i.p.with 0.2 ml sterile saline solution(0.85%,w/v).Three bullfrogs in both groups were sampled at 0,1,3,7,11,15 and 20 days post-injection(dpi) for the evaluation of non-specific immune parameters.It was observed that intraperitoneal injection of A.hydrophila significantly increased the number of leucocytes and that of NBT-positive cells in peripheral blood.Significant increases in serum bactericidal activity and serum acid phosphatase activity were also observed in the bacterium-injected frogs when compared with those in the control group.However,a significant reduction was detected in vitro in phagocytosis activity of peripheral blood phagocytes.No significant difference in changes in the number of peripheral erythrocytes,serum superoxide dismutase(SOD) activity,and lysozyme activity was detected between the two groups.It is suggested that bullfrogs may produce a series of non-specific immune reactions in response to the A.hydrophila infection.

Role of inflammasome regulation on immune modulators

Inflammatory responses are essential in eliminating harmful substrates from damaged tissue and inducing recovery.Several cytokines participate in and facilitate this response. Certain cytokines such as interleukin(IL)-1β and IL-18 are initially produced in precursor form in response to toll-like receptor(TLR) ligands and undergo maturation by inflammasomes, which are cytosolic multi-protein complexes containing nucleotide-binding oligomerization domain(NOD)-containing protein 2-like receptors(NLRs). Immune modulators targeting inflammasomes have been investigated to control inflammatory diseases such as metabolic syndrome. However, most immune modulators possessing anti-inflammasome properties attenuate production of other cytokines, which are essential for host defense. In this review, we analyzed the effect of anti-inflammasome agents on the production of cytokines which are not regulated by inflammasome and involving in initial immune responses. As a result, the infiammasome inhibitors are put into three categories: non-effector, stimulator, or inhibitor of cytokine production. Even the stimulator of cytokine production ameliorated symptoms resulting from inflammasome activation in mouse models. Thus, we suggest ideal immune modulators targeting inflammasomes in order to enhance cytokine production while inhibiting cytokine maturation.

Effect of Dietary Alanyl-glutamine Supplementation on Growth Performance, Development of Intestinal Tract, Antioxidant Status and Plasma Non-specific Immunity of Young Mirror Carp(Cyprinus carpio L.)

Exogenous alanyl-glutamine（Aln-Gln） was evaluated for its effects on growth performance, intestinal structure and function, antioxidant status and non-specific immunity of young carp（Cyprinus carpio L.）. Six diets supplemented with 0, 2.5, 5.0, 7.5, 10.0, or 15.0 g · kg-1 of Aln-Gln were fed to fish for 12 weeks. Supplementation with 7.5, 10.0, or 15.0 g · kg-1 of Aln-Gln significantly increased weight gain rate（WGR）, protein efficiency ratio（PER）, but feed conservation rate（FCR） and survival were not affected（P〉0.05）. The intestinal fold height and number, digestive enzyme, Na＋, K＋-ATPase activities was found to be significantly high（P〈0.05） with increasing dietary Aln-Gln supplementation up to 7.5 g · kg-1, but there were no significant differences for Aln-Gln supplementation from 7.5 to 15.0 g · kg-1. The glutathione peroxidase（GPX） activity, glutathione（GSH）, superoxide dismutase（SOD） activity increased and malondialdehyde（MDA） levels decreased significantly（P〈0.05） in the intestine, hepatopancreas, plasma and muscles. The plasma complement-3（C3） and complement-4（C4） levels were significantly（P〈0.05） improved at 5.0 g · kg-1 level and decreased when over 7.5 g · kg-1. The plasma lysozyme（LSZ） activity increased significantly（P〈0.05） at 7.5, 10.0, or 15.0 g · kg-1 level. In summary, the results showed that Aln-Gln improved growth performance, development and function of the intestine, the activity of the antioxidant defense system and the plasma non-specific immunity of the carps. The optimal Aln-Gln level was 8.24 g · kg-1 diet for WGR based on broken-line regression model analysis.

Effects of Size Grading on Growth and Non-Specific Immunity Factors of the Shrimp Litopenaeus vannamei Boone

The study aims to determine the effects of graded farming on growth performance and non-specific immunity factors of shrimp Litopenaeus vannamei Boone. Three size groups of shrimp, i.e., the small size group [Gs, with an average body length （BL） of （3.04 ± 0.36） cm and body weight （BW） （0.412± 0.35） g], the large group [GL, with a BL of （4.29±0.55） cm and BW of （1.098 ±0.42） g], and the ungraded group [Gm, with a BL of （3.47±0.81） cm and BW of （0.611 ±0.79） g], were reared under the same conditions for 8 wk. Growth performance and non- specific immunity factors were measured. The results showed that BW gain, biomass gain and the specific growth rate of body length （SGRL） were significantly influenced by size grading （one-way ANOVA, P 〈 0.05）. The peroxidase （POD） and antibacterial （Ua） activities of GL were lower than those of G. Superoxide dismutase （SOD） and lysozyme （U1） activities of Gm were lower than those of G. No significant difference （P = 0.121 〉 0.05） was found on phenoloxidase （PO） activity among the three size groups. Synthetically, size grading could enhance growth and rearing efficiency, and did not have a significant influence on the immunity of L. vannamei Boone. Therefore, graded fanning in L. vannamei Boone was feasible in the culture practice.

Immune-modulating therapy in acute pancreatitis:Fact or fiction

Acute pancreatitis(AP) is one of the most common diseases of the gastrointestinal tract,bearing significant morbidity and mortality worldwide.Current treatment of AP remains unspecific and supportive and is mainly targeted to aggressively prevent systemic complications and organ failure by intensive care.As acute pancreatitis shares an indistinguishable profile of inflammation with sepsis,therapeutic approaches have turned towards modulating the systemic inflammatory response.Targets,among others,have included pro- and antiinflammatory modulators,cytokines,chemokines,immune cells,adhesive molecules and platelets.Even though,initial results in experimental models have been encouraging,clinical implementation of immuneregulating therapies in acute pancreatitis has had a slow progress.Main reasons include difficulty in clinical translation of experimental data,poor understanding of inflammatory response time-course,flaws in experimental designs,need for multimodal approaches and commercial drawbacks.Whether immune-modulation in acute pancreatitis remains a fact or just fiction remains to be seen in the future.

Role of gut microbiota and Helicobacter pylori in inflammatory bowel disease through immune-mediated synergistic actions

A recent study published in the World Journal of Gastroenterology,suggests that transplanting the gut microbiota from healthy donors can alleviate the pathological processes linked to inflammatory bowel disease(IBD),particularly Crohn's disease.In addition,that paper illustrates the effect of changes in the gut microbiota on IBD and points out that altered mesenteric adipose tissue caused by the gut microbiota and creeping fat lead to increased inflammation,which exacerbates IBD.Moreover,recent research has shown that the interaction between Helicobacter pylori(H.pylori)and the gut microbiota is mediated through immune mechanisms,resulting in a synergistic impact on IBD.Therefore,in this manuscript,we will focus on the role of the gut microbiota and H.pylori in the immune response to IBD,as well as the possible impact of H.pylori on the gut microbiota.We will also explore their individual and synergistic immune effects on IBD and look at future therapeutic perspectives for IBD.

Effects of the Chinese Medicinal Herb Com plex Additives on Non-specific Immunity of Amursturgeon( Acipenser schrencki Brandt)

This study was to investigate the effects of aqueous decotion from three Chinese medicinal herb additives （ Cyrtomium fortunei, prescription I and prescription II） on non-specific immunity of 1 ＋ age old Amur sturgeon （Acipenser schrencki Brandt） by oral perfusion. Cyrtomiumfortunei, prescription I and prescription II were orally given to 15 fishes for each experimental group once a day, with the concentration of 9,175 and 36 g/S0 kg body weight, respectively. The administration was lasted for 14 days. Meanwhile, distilled water was orally given as the control. After the experiment, some of the experimental fishes were stimulated with high temperature （30 ℃ ） for two hours. Sampling was performed from fishes treated at 22 ℃ and 30 ℃ for measuring the protein content in the serum, phagocytic activity of leucocytes and the activity of the lysozyme in six tissues. The results indicated that Cyrtomiumfortunei and prescription II could help to enhance the content of various proteins and the phagocytic activity of leucocytes. There was no significant change in the effects between these two additives at either the normal temperature or high temperature. Prescription I did not show an obvious effect on the immunity of fishes at the normal temperature, but it did in promo- ting high-efficiency response and improving immunoregulation of fish shocked by some stimuli.

Harnessing immunity:Immunomodulatory therapies in COVID-19

An overly exuberant immune response,characterized by a cytokine storm and uncontrolled inflammation,has been identified as a significant driver of severe coronavirus disease 2019(COVID-19)cases.Consequently,deciphering the intricacies of immune dysregulation in COVID-19 is imperative to identify specific targets for intervention and modulation.With these delicate dynamics in mind,immunomodulatory therapies have emerged as a promising avenue for miti-gating the challenges posed by COVID-19.Precision in manipulating immune pathways presents an opportunity to alter the host response,optimizing antiviral defenses while curbing deleterious inflammation.This review article compre-hensively analyzes immunomodulatory interventions in managing COVID-19.We explore diverse approaches to mitigating the hyperactive immune response and its impact,from corticosteroids and non-steroidal drugs to targeted biologics,including anti-viral drugs,cytokine inhibitors,JAK inhibitors,convalescent plasma,monoclonal antibodies(mAbs)to severe acute respiratory syndrome coronavirus 2,cell-based therapies(i.e.,CAR T,etc.).By summarizing the current evidence,we aim to provide a clear roadmap for clinicians and researchers navigating the complex landscape of immunomodulation in COVID-19 treatment.CS Glucocorticoids are among the most widely prescribed drugs with their immune-suppressive and anti-inflammatory effect[84].The current guidelines for the treatment of COVID-19 recommend against the use of dexamethasone or other systemic CS in non-hospitalized patients in the absence of another indication[70].The RECOVERY trial demonstrates the reduced 28-d mortality among hospitalized patients with COVID-19 using dexamethasone compared to the usual standard of care,along with other investigators,such as Ahmed and Hassan[85].The benefit of dexamethasone was seen only among participants receiving either oxygen alone or invasive mechanical ventilation at randomization but not among those receiving no respiratory support at enrollment[85].In a systematic review and meta-analysis,Albuquerque et al[86]showed that in comparison to tocilizumab,baricitinib,and sarilumab are associated with high probabilities of similar mortality reductions among hospitalized COVID-19 concurrently treated with CS.As a result of the absence of SARS-CoV-2-specific antiviral medications,the effectiveness of COVID-19 treatments is reduced.Several COVID-19 therapies are now under investigation.However,the majority of them lack specificity,efficacy,and safety[87].Immunotherapy is a ground-breaking medical treatment that manipulates the immune system to fight diseases.Translational research is rapidly progressing,recognized as a significant breakthrough in 2013[88].Among the immunotherapeutic options for treating COVID-19 are Immunoglobulin,CP,antibodies,mAbs(mAbs),NK cells,T cells,TLR,cytokine therapies and immune modulators.

Effect of Ammonia-Nitrogen Stress on Non-specific Immunity of Hybrid Tilapia(Oreochromis niloticus× Oreochromis areus)

The juveniles of hybrid tilapia （ Oreochromis niloticus x Oreochromis areus） were exposed to ananonia-nitrogen （N） （0, 2.5, 5, 10 and 20 mg/L） for 0, 12, 24, 48 and 72 h to evaluate the effect of ammonia-N stress on their non-specific immunity. Results show that the activity of serum lysozyme decreased signifi- candy with extension of stress time （P 〈 0.05）. The total antioxidant capacity （T-AOC） and activity of antioxidase in liver were significantly affected. The activi- ty of T-AOC and total superoxide dismutase （T-SOD） of fish exposed to ammonia-N were initially decreasing then increasing （ P 〈 0.05 ）. Activities of catalase （CAT） and glutathione peroxidase （GSH-Px） were correlated with concentrations of ammonia-N. Fish exposed to lower concentrations （2.5 mg/L or 5 mg/L） showed decreased CAT activity within 24 h （P 〈 0.05 ）, while those exposed to higher concentrations （10 mg/L or 20 mg/L） initially showed increased then decreased activity of CAT. Except for the highest concentration groups, fish exposed to ammonia-N showed inductive activity of GSH-Px （ P 〈 0.05 ）. Under the ex- perimental conditions, non-specific immunity of tilapia was affected by ammonia-N stress, and the impact was increased with increased concentration and extension of time.

Cation-anionicpalladium Complexes—New Types of Antitumor, Immune Response-modulating and Radioprotective Agents

Here we report results of our investigations of new class of bioactive palladium compounds (AH n ) m [PdCl 4 ], which were discovered as a result of systematic study of correlations between composition, structure and bioactivity of different types of platinum metals coordination compounds. For the first time we demonstrated in vivoa possibility of development of palladium compounds, which exceed cisplatin in antitumor activity and do not show immunosuppressive effects, and palladium compounds with immunostimulating and radioprotective activities. Combinations of cytostatic agents or radiation with palladium complexes lead to significant synergism of their activities and high therapeutic efficiency exceeded an efficiency of their separated use.

Effect of Astragalus polysaccharides on Erythrocyte Immune Adherence of Chickens Inoculated with Infectious Bursal Disease Virus

Two hundred and forty specific pathogen free leghorn chickens were randomly divided into four groups and reared in isolated pens. The tested chickens were negative to infectious bursal disease virus （IBDV） at 25 d old. Group 1 was treated with saline, whereas Groups 2, 3, and 4 were inoculated with 0.3 mL IBDV suspension intranasally the next day. Groups 3 and 4 were also administered with Astragalus polysaccharides （APS） intramuscularly twice daily at 5 or 10 mg kg-1 BW, respectively, until 31 d old. The erythrocyte-C3b receptor rosette rate （E-C3bRR） and the erythrocyte-C3b immune complex rosette rate （E-ICRR） were measured at 25, 29, 32, 35, and 38 d old. The results showed that IBDV significantly reduced E-C3bRR and E-ICRR when compared with the control group （P 〈 0.05）, while simultaneous administration of APS with 1BDV maintained E-C3bRR at similar levels to the control group （P 〉 0.05） and increased E-ICRR when compared with the control group and the group non-treated with APS （P 〈 0.05）. APS treatment reduced the morbidity and mortality of chickens inoculated with IBDV （P 〈 0.05）. The results suggest that APS may enhance the immune adherence of chickens erythrocytes by affecting the activity and/or the number of complement receptors on the erythrocyte membrane. These findings can be beneficial in providing an understanding of the basic mechanisms required for the rational application of APS in modern medicine.

Probiotic modulation of dendritic cells co-cultured with intestinal epithelial cells

AIM： To investigate cytokine production and cell surface phenotypes of dendritic cells （DC） in the presence of epithelial cells stimulated by probiotics.METHODS： Mouse DC were cultured alone or together with mouse epithelial cell monolayers in normal or in- verted systems and were stimulated with heat-killed probiotic bacteria, Bifidobacterium lactis ADO 11 （BL）, Bifidobacterium bilfidum BGN4 （BB）, Lactobacillus casei IBS041 （LC）, and Lactobacillus acidophilus AD031 （LA）, for 12 h. Cytokine levels in the culture supernatants were determined by enzyme-linked immunosorbent as say and phenotypic analysis of DC was investigated by flow cytometry.RESULTS： BB and LC in singlecultured DC increased the expression of I-Ad, CD86 and CD40 （I-Ad, 18.51 vs 30.88, 46.11, CD86, 62.74 vs 92.7, 104.12; CD40, 0.67 vs 6.39, 3.37, P 〈 0.05）. All of the experimental probiot-ics increased the production of inflammatory cytokines, interleukin （IL）-6 and tumor necrosis factor （TNF）-α. However, in the normal coculture systems, LC and LA decreased the expression of I-A^α （39.46 vs 30.32, 33.26, P 〈 0.05）, and none of the experimental probiotics increased the levels of IL-6 or TNF-α. In the inverted coculture systems, LC decreased the expression of CD40 （1.36 vs -2.27, P 〈 0.05）, and all of the experimental probiotics decreased the levels of IL-6. In addition, BL increased the production of IL-10 （103.8 vs 166.0, P 〈 0.05） and LC and LA increased transforming growth factor-13 secretion （235.9 vs 618.9, 607.6, P 〈 0.05）.CONCLUSION： These results suggest that specific pro- biotic strains exert differential immune modulation mediated by the interaction of dendritic cells and epithelial cells in the homeostasis of gastrointestinal tract.

Clinical development of reovirus for cancer therapy:An oncolytic virus with immune-mediated antitumor activity

Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle. Reovirusmediated immune responses can present barriers to tumor targeting, serve protective functions against reovirus systemic toxicity, and contribute to therapeutic efficacy through antitumor immune-mediated effects via innate and adaptive responses. Preclinical studies have demonstrated the broad anticancer activity of wild-type, unmodified type 3 Dearing strain reovirus（Reolysin） across a spectrum of malignancies. The development of reovirus as an anticancer agent and available clinical data reported from 22 clinical trials will be reviewed.

Effects of Methionine on the Immune Function in Animals

Nutrition and immunity are the hot topics in animal’s production, and the effects of methionine on the immunity are already confirmed as the deep research on the nutrition of amino acid and immune function. However, the relationship of the methionine and immunity has not been elucidated clearly, this review aims to clarify the effects of methionine on immune function in the aspects of growth and development immune organs, the histological structure of the immune organs, non-specific immunity, humoral immunity, cellular immunity and cytokines, and to provide foundations for further studies on the relationship between methionine and immune function.

Radiotherapy as an immune checkpoint blockade combination strategy for hepatocellular carcinoma

In the immune oncology era,the clinical efficacy of immune checkpoint inhibitors(ICIs)against most solid cancers is well known.In hepatocellular carcinoma,the recent success of combination therapy with targeting agents has accelerated the search for novel combination strategies.Radiotherapy(RT),an attractive modality,can be combined with ICIs,which act as strong modulators of the tumor immune microenvironment.Herein,we discuss immune modulation caused by radiation and the current trials of RT-ICI combination treatment as well as future perspectives.