Low skeletal muscle mass and high visceral adiposity are associated with recurrence of acute cholecystitis after conservative management:A propensity score-matched cohort study

Background:Recurrent acute cholecystitis(RAC)can occur after non-surgical treatment for acute cholecystitis(AC),and can be more severe in comparison to the first episode of AC.Low skeletal muscle mass or adiposity have various effects in several diseases.We aimed to clarify the relationship between RAC and body parameters.Methods:Patients with AC who were treated at our hospital between January 2011 and March 2022 were enrolled.The psoas muscle mass and adipose tissue area at the third lumbar level were measured using computed tomography at the first episode of AC.The areas were divided by height to obtain the psoas muscle mass index(PMI)and subcutaneous/visceral adipose tissue index(SATI/VATI).According to median VATI,SATI and PMI values by sex,patients were divided into the high and low PMI groups.We performed propensity score matching to eliminate the baseline differences between the high PMI and low PMI groups and analyzed the cumulative incidence and predictors of RAC.Results:The entire cohort was divided into the high PMI(n=81)and low PMI(n=80)groups.In the propensity score-matched cohort there were 57 patients in each group.In Kaplan-Meier analysis,the low PMI group and the high VATI group had a significantly higher cumulative incidence of RAC than their counterparts(log-rank P=0.001 and 0.015,respectively).In a multivariate Cox regression analysis,the hazard ratios of low PMI and low VATI for RAC were 5.250(95%confidence interval 1.083-25.450,P=0.039)and 0.158(95%confidence interval:0.026-0.937,P=0.042),respectively.Conclusions:Low skeletal muscle mass and high visceral adiposity were independent risk factors for RAC.

Duplicated gallbladder with acute cholecystitis:a case of unusual presentation and diagnostic challenges

Anomalies in the gallbladder can lead to misidentifying anatomical structures,heightening the risk of complications in laparoscopic and open cholecystectomy procedures.Failure to recognize these variations increases the chances of iatrogenic bile duct injuries and other complications.

Evaluating effectiveness and safety of combined percutaneous transhepatic gallbladder drainage and laparoscopic cholecystectomy in acute cholecystitis patients:Meta-analysis

BACKGROUND Acute cholecystitis(AC)is a common disease in general surgery.Laparoscopic cholecystectomy(LC)is widely recognized as the"gold standard"surgical procedure for treating AC.For low-risk patients without complications,LC is the recommended treatment plan,but there is still controversy regarding the treatment strategy for moderate AC patients,which relies more on the surgeon's experience and the medical platform of the visiting unit.Percutaneous transhepatic gallbladder puncture drainage(PTGBD)can effectively alleviate gallbladder inflammation,reduce gallbladder wall edema and adhesion around the gallbladder,and create a"time window"for elective surgery.AIM To compare the clinical efficacy and safety of LC or PTGBD combined with LC for treating AC patients,providing a theoretical basis for choosing reasonable surgical methods for AC patients.METHODS In this study,we conducted a clinical investigation regarding the combined use of PTGBD tubes for the treatment of gastric cancer patients with AC.We performed searches in the following databases:PubMed,Web of Science,EMBASE,Cochrane Library,China National Knowledge Infrastructure,and Wanfang Database.The search encompassed literature published from the inception of these databases to the present.Subsequently,relevant data were extracted,and a meta-analysis was conducted using RevMan 5.3 software.RESULTS A comprehensive analysis was conducted,encompassing 24 studies involving a total of 2564 patients.These patients were categorized into two groups:1371 in the LC group and 1193 in the PTGBD+LC group.The outcomes of the meta-analysis revealed noteworthy disparities between the PTGBD+LC group and the LC group in multiple dimensions:(1)Operative time:Mean difference(MD)=17.51,95%CI:9.53-25.49,P<0.01;(2)Conversion to open surgery rate:Odds ratio(OR)=2.95,95%CI:1.90-4.58,P<0.01;(3)Intraoperative bleeding loss:MD=32.27,95%CI:23.03-41.50,P<0.01;(4)Postoperative hospital stay:MD=1.44,95%CI:0.14-2.73,P=0.03;(5)Overall postoperative compli-cation rate:OR=1.88,95%CI:1.45-2.43,P<0.01;(6)Bile duct injury:OR=2.17,95%CI:1.30-3.64,P=0.003;(7)Intra-abdominal hemorrhage:OR=2.45,95%CI:1.06-5.64,P=0.004;and(8)Wound infection:OR=0.These find-ings consistently favored the PTGBD+LC group over the LC group.There were no significant differences in the total duration of hospitalization[MD=-1.85,95%CI:-4.86-1.16,P=0.23]or bile leakage[OR=1.33,95%CI:0.81-2.18,P=0.26]between the two groups.CONCLUSION The combination of PTGBD tubes with LC for AC treatment demonstrated superior clinical efficacy and enhanced safety,suggesting its broader application value in clinical practice.

Assessment of systemic immune-inflammatory index and other inflammatory parameters in predicting mortality in patients with acute cholecystitis:A retrospective observational study

Objective:To investigate the effectiveness of the systemic immune-inflammatory(SII)index and other inflammatory parameters in predicting mortality among patients with acute cholecystitis(AC).Methods:279 Patients presented to the emergency department with abdominal pain and diagnosis of AC between September 2021 and September 2023 were included in the study.Demographic data,laboratory parameters,clinical follow-ups,and outcomes of the patients were recorded.Results:The mean age of the patients was(55.0±16.3)years and 36.6%were male.63.8%Had gallbladder/choledochal stones and 49.5%underwent surgery.The mortality rate was 6.1%.Advanced age(P=0.170)and prolonged hospitalization(P=0.011)were statistically significant risk factors for mortality.Decreased lymphocyte count(P=0.020)and increased C-reactive protein(CRP)levels(P=0.033)were found to be risk factors for mortality.According to the mortality predictor ROC analysis results,the cut-off for SII index was 3138(AUC=0.817,sensitivity=70.5%,specificity=84.7%),the cut-off for neutrophil count was 15.28×10^(3)/mm^(3)(AUC=0.761,sensitivity=52.9%,specificity=95.0%),the cut-off for leukocyte count was 19.0×10^(3)/mm^(3)(AUC=0.714,sensitivity=52.9%,specificity=98.0%),cut-off for CRP was 74.55(AUC=0.758,sensitivity=70.5%,specificity=79.0%),cut-off for aspartate transaminase(AST)was 33.0 IU/L(AUC=0.658,sensitivity=82.3%,specificity=50.3%).Conclusions:The SII index may be a good predictor of mortality with high sensitivity and specificity.Elevated levels of neutrophils,leukocytes,CRP,and AST are other inflammatory parameters that can be used to predict mortality associated with AC.

Effect of surgical timing on postoperative outcomes in patients with acute cholecystitis after delayed percutaneous transhepatic gallbladder drainage

BACKGROUND To date,the optimal timing for percutaneous transhepatic gallbladder drainage(PTGBD),particularly for patients who have missed the optimal window for emergency laparoscopic cholecystectomy(LC)(within 72 hours of symptom onset)has not been determined.AIM To study the effects of LC timing on outcomes of grade II/III acute cholecystitis(AC)in patients with delayed PTGBD.METHODS Data of patients diagnosed with Tokyo Guidelines 2018 grade II or III AC who underwent delayed PTGBD followed by LC at a single hospital between 2018 and 2022 were retrospectively studied.According to the interval between gallbladder drainage and cholecystectomy,the patients were divided into early and delayed LC groups.Outcomes including surgery time,postoperative complications and hospital stay,and patient satisfaction were analyzed and compared between the two groups using t-andχ^(2) tests.RESULTS There were no significant differences between the two groups in intraoperative blood loss,postoperative abdominal drainage tube placement time,pain index,or total disease duration(all P>0.05).Compared with those of the early LC group,the delayed group showed significant decreases in the length of procedure(surgery time),conversion rate to open surgery,degree of adhesions,surgical complications,postoperative hospital stay,and total treatment costs,and increased patient satisfaction despite a longer interval before PTGBD(all P<0.05).CONCLUSION For patients with grade II/III AC with delayed PTGBD,LC should be performed 2 weeks after PTGBD to decrease postoperative complications and hospital stays and improve patient satisfaction.

Hepatitis A virus-associated acute acalculous cholecystitis in an adult-onset Still’s disease patient:A case report and review of the literature

BACKGROUND Acute acalculous cholecystitis(AAC)is inflammation of the gallbladder without evidence of calculi.Although rarely reported,its etiologies include hepatitis virus infection(e.g.,hepatitis A virus,HAV)and adult-onset Still’s disease(AOSD).There are no reports of HAV-associated AAC in an AOSD patient.CASE SUMMARY Here we report a rare case of HAV infection-associated AAC in a 39-year-old woman who had a history of AOSD.The patient presented with an acute abdomen and hypotension.Elevated hepatobiliary enzymes and a thickened and distended gallbladder without gallstones on ultrasonography suggested AAC,but there were no signs of anemia nor thrombocytopenia.Serological screening revealed anti-HAV IgM antibodies.Steroid treatment did not alleviate her symptoms,and she was referred for laparoscopic cholecystectomy.The resected gallbladder was hydropic without perforation,and her clinical signs gradually improved after surgery.CONCLUSION AAC can be caused by HAV in AOSD patients.It is crucial to search for the underlying etiology for AAC,especially uncommon viral causes.

Impact of interstitial cells of Cajal on slow wave and gallbladder contractility in a guinea pig model of acute cholecystitis

BACKGROUND Impaired interstitial cells of Cajal(ICCs)are central to the pathophysiology of acute cholecystitis(AC).Common bile duct ligation is a common model of AC,producing acute inflammatory changes and decrease in gallbladder contractility.AIM To investigate the origin of slow wave(SW)in the gallbladder and the effect of ICCs on gallbladder contractions during the process of AC.METHODS Methylene blue(MB)with light was used to establish selective impaired ICCs gallbladder tissue.Gallbladder motility was assessed using the frequency of SW and gallbladder muscle contractility in vitro in normal control(NC),AC12h,AC24h,and AC48h groups of guinea pigs.Hematoxylin and eosin and Massonstained gallbladder tissues were scored for inflammatory changes.ICCs pathological changes alterations were estimated using immunohistochemistry and transmission electron microscopy.The alterations of c-Kit,α-SMA,cholecystokinin A receptor(CCKAR),and connexin 43(CX43)were assessed using Western blot.RESULTS Impaired ICCs muscle strips resulted in the decrease in gallbladder SW frequency and contractility.The frequency of SW and gallbladder contractility were significantly lower in the AC12h group.Compared with the NC group,the density and ultrastructure of ICCs were remarkably impaired in the AC groups,especially in the AC12h group.The protein expression levels of c-Kit were significantly decreased in the AC12h group,while CCKAR and CX43 protein expression levels were significantly decreased in the AC48h group.CONCLUSION Loss ICCs could lead to a decrease in gallbladder SW frequency and contractility.The density and ultrastructure of ICCs were clearly impaired in the early stage of AC,while CCKAR and CX43 were significantly reduced at end stage.

Revolutionizing gastric cancer treatment:The potential of immunotherapy

Gastric cancer,a prevalent malignancy worldwide,ranks sixth in terms of frequency and third in fatality,causing over a million new cases and 769000 annual deaths.Predominant in Eastern Europe and Eastern Asia,risk factors include family medical history,dietary habits,tobacco use,Helicobacter pylori,and Epstein-Barr virus infections.Unfortunately,gastric cancer is often diagnosed at an advanced stage,leading to a grim prognosis,with a 5-year overall survival rate below 5%.Surgical intervention,particularly with D2 Lymphadenectomy,is the mainstay for early-stage cases but offers limited success.For advanced cases,the National Comprehensive Cancer Network recommends chemotherapy,radiation,and targeted therapy.Emerging immunotherapy presents promise,especially for unresectable or metastatic cases,with strategies like immune checkpoint inhibitors,tumor vaccines,adoptive immunotherapy,and nonspecific immunomodulators.In this Editorial,with regards to the article“Advances and key focus areas in gastric cancer immunotherapy:A comprehensive scientometric and clinical trial review”,we address the advances in the field of immunotherapy in gastric cancer and its future prospects.

Pathologically successful conversion hepatectomy for advanced giant hepatocellular carcinoma after multidisciplinary therapy:A case report and review of literature

BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.

Xanthogranulomatous cholecystitis managed by laparotomy may go through troublesome clinical course: Reflection of severe inflammation

To the Editor: Xanthogranulomatous cholecystitis(XGC) is an uncommon inflammatory disease of the gallbladder, and its incidence is reported to be 1.3%-5.2% [1]. XGC is diagnosed by histopathological examination, characterized by severe inflammatory destruction followed by a granulomatous reaction, marked proliferative fibrosis, and infiltration of inflammatory cells [2].

Necrotizing Fasciitis Secondary to Emphysematous Cholecystitis and Cholecystocutaneous Fistula: A Rare Case Report Presentation

Emphysematous cholecystitis is a rare subtype of acute cholecystitis characterized by the presence of gas in the gallbladder wall secondary to ischemia. Typically, this is a result of cystic artery vascular compromise with a concomitant infection from gas-forming organisms such as Clostridium species, Klebsiella species, or Escherichia coli. The mortality rate of acute emphysematous cholecystitis is 15% - 20% compared with 1.4% in uncomplicated acute cholecystitis. The subsequent development of a cholecystocutaneous fistula, an abnormal connection between the gallbladder and the skin, is also a rare complication of gallbladder disease. We describe a case of a 77-year-old male who presented with right flank necrotizing fasciitis which developed from a cholecystocutaneous fistula secondary to emphysematous cholecystitis. Once the necrotic tissues were adequately debrided, the large open wound was treated with negative pressure wound therapy with instillation (NPWT-i) utilizing hypochlorous acid (HOCL). The wound was closed with a split-thickness skin graft.

Acute Alithiasis Cholecystitis in Children: Diagnostic and Therapeutic Approach in the Pediatric Surgery Department of the CHU of Conakry

Acute alithiasic cholecystitis (AAC) is the inflammatory disease of the gallbladder in the absence of gallstones. It is a rare pathology in children. The aim was to describe the clinical, diagnostic and therapeutic characteristics of this disease. Materials and Method: This was a 3-year retrospective study (January 2008 to December 2010) including 66 patient records collected for CAA. Results: The frequency of AAC was 3.57%, the mean age of the patients was 8 ± 3.52 years, and there were 36 boys and 30 girls. The main clinical features were right hypochondrial pain (66 cases), positive Murphy’s (66 cases), fever (53 cases) and jaundice or sub-jaundice (51 cases). The main ultrasound signs were thickened vesicular wall 50 cas (75.76%), vesicular distension 50cas (75.76%) and positive ultrasound Murphy 47 cas (71.21%). Medical treatment was exclusive in 64 patients (96.97%) and surgical treatment in 2 patients (3.03%). Conclusion: Acute alithiasic cholecystitis is a rare pathology in children, the clinical picture is not very specific and abdominal ultrasound is the key to early diagnosis. Conservative treatment is the first choice in the absence of any complications.

PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma:A case report

BACKGROUND Pancreatic ductal adenocarcinoma(PDAC)is a highly fatal disease with limited effective treatment especially after first-line chemotherapy.The human epidermal growth factor receptor 2(HER-2)immunohistochemistry(IHC)positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC.CASE SUMMARY We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn’t have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment.A novel combination therapy PRaG 3.0 of RC48(HER2-antibody-drug conjugate),radio-therapy,PD-1 inhibitor,granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month.She had not developed any grade 2 or above treatment-related adverse events at any point.Percentage of peripheral CD8^(+) Temra and CD4^(+) Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy.CONCLUSION PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Immunotherapy for esophageal cancer:Where are we now and where can we go

Immune checkpoint inhibitor therapy has dramatically improved patient prognosis,and thereby transformed the treatment in various cancer types including esophageal squamous cell carcinoma(ESCC)in the past decade.Monoclonal antibodies that selectively inhibit programmed cell death-1(PD-1)activity has now become standard of care in the treatment of ESCC in metastatic settings,and has a high expectation to provide clinical benefit during perioperative period.Further,anti-cytotoxic T-lymphocyte–associated protein 4(CTLA-4)monoclonal antibody has also been approved in the treatment of recurrent/metastatic ESCC in combination with anti-PD-1 antibody.Well understanding of the existing evidence of immune-based treatments for ESCC,as well as recent clinical trials on various combinations with chemotherapy for different clinical settings including neoadjuvant,adjuvant,and metastatic diseases,may provide future prospects of ESCC treatment for better patient outcomes.

Present and future of new systemic therapies for early and intermediate stages of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a high mortality neoplasm which usually appears on a cirrhotic liver.The therapeutic arsenal and subsequent prognostic outlook are intrinsically linked to the HCC stage at diagnosis.Notwithstanding the current deployment of treatments with curative intent(liver resection/local ablation and liver transplantation)in early and intermediate stages,a high rate of HCC recurrence persists,underscoring a pivotal clinical challenge.Emergent systemic therapies(ST),particularly immunotherapy,have demonstrate promising outcomes in terms of increase overall survival,but they are currently bound to the advanced stage of HCC.This review provides a comprehensive analysis of the literature,encompassing studies up to March 10,2024,evaluating the impact of novel ST in the early and intermediate HCC stages,specially focusing on the findings of neoadjuvant and adjuvant regimens,aimed at increasing significantly overall survival and recurrence-free survival after a treatment with curative intent.We also investigate the potential role of ST in enhancing the downstaging rate for the intermediate-stage HCC initially deemed ineligible for treatment with curative intent.Finally,we critically discuss about the current relevance of the results of these studies and the encouraging future implications of ST in the treatment schedules of early and intermediate HCC stages.

Back to the drawing board:Overview of the next generation of combination therapy for inflammatory bowel disease

Inflammatory bowel disease(IBD)is entering a potentially new era of combined therapeutics.Triantafillidis et al provide an insightful review of the current state of combination therapy,with a focus on the use of a combined biologic and immunomodulator,as well as emerging data on the future potential of dual-biologic therapy(DBT).While current evidence for DBT is limited,encouraging safety profiles and ongoing trials suggest a brighter future for this approach.The importance of controlled trials should be stressed in establishing new treatment paradigms.Ongoing prospective randomized trials of DBT and perhaps future combinations of biologics and small molecule therapies will hopefully guide the next generation of IBD care.

Adjuvant therapy for hepatocellular carcinoma:Dilemmas at the start of a new era

Approximately 50%-70%of patients with hepatocellular carcinoma experience recurrence within five years after curative hepatic resection or ablation.As a result,many patients receive adjuvant therapy after curative resection or ablation in order to prolong recurrence-free survival.The therapy recommended by national guidelines can differ,and guidelines do not specify when to initiate adjuvant therapy or how long to continue it.These and other unanswered questions around adjuvant therapies make it difficult to optimize them and determine which may be more appropriate for a given type of patient.These questions need to be addressed by clinicians and researchers.

A Stable Open-Shell Conjugated Diradical Polymer with Ultra-High Photothermal Conversion Efficiency for NIR-Ⅱ Photo-Immunotherapy of Metastatic Tumor

Massive efforts have been concentrated on the advance of eminent near-infrared(NIR) photothermal materials(PTMs) in the NIR-Ⅱ window(1000–1700 nm), especially organic PTMs because of their intrinsic biological safety compared with inorganic PTMs. However, so far, only a few NIR-Ⅱresponsive organic PTMs was explored, and their photothermal conversion efficiencies(PCEs) still remain relatively low. Herein, donor–acceptor conjugated diradical polymers with open-shell characteristics are explored for synergistically photothermal immunotherapy of metastatic tumors in the NIR-Ⅱ window. By employing side-chain regulation, the conjugated diradical polymer TTB-2 with obvious NIR-Ⅱ absorption was developed, and its nanoparticles realize a record-breaking PCE of 87.7% upon NIR-Ⅱ light illustration. In vitro and in vivo experiments demonstrate that TTB-2 nanoparticles show good tumor photoablation with navigation of photoacoustic imaging in the NIR-Ⅱ window, without any side-effect. Moreover, by combining with PD-1 antibody,the pulmonary metastasis of breast cancer is high-effectively prevented by the efficient photo-immunity effect. Thus, this study explores superior PTMs for cancer metastasis theranostics in the NIR-Ⅱ window, offering a new horizon in developing radical-characteristic NIR-Ⅱ photothermal materials.

Optimized sequential therapy vs 10- and 14-d concomitant therapy for eradicating Helicobacter pylori: A randomized clinical trial

BACKGROUND A cure for Helicobacter pylori(H.pylori)remains a problem of global concern.The prevalence of antimicrobial resistance is widely rising and becoming a challenging issue worldwide.Optimizing sequential therapy seems to be one of the most attractive strategies in terms of efficacy,tolerability and cost.The most common sequential therapy consists of a dual therapy[proton-pump inhibitors(PPIs)and amoxicillin]for the first period(5 to 7 d),followed by a triple therapy for the second period(PPI,clarithromycin and metronidazole).PPIs play a key role in maintaining a gastric pH at a level that allows an optimal efficacy of antibiotics,hence the idea of using new generation molecules.This open-label prospective study randomized 328 patients with confirmed H.pylori infection into three groups(1:1:1):The first group received quadruple therapy consisting of twice-daily(bid)omeprazole 20 mg,amoxicillin 1 g,clarith-romycin 500 mg and metronidazole 500 mg for 10 d(QT-10),the second group received a 14 d quadruple therapy following the same regimen(QT-14),and the third group received an optimized sequential therapy consisting of bid rabe-prazole 20 mg plus amoxicillin 1 g for 7 d,followed by bid rabeprazole 20 mg,clarithromycin 500 mg and metronidazole 500 mg for the next 7 d(OST-14).AEs were recorded throughout the study,and the H.pylori eradication rate was determined 4 to 6 wk after the end of treatment,using the 13C urea breath test.RESULTS In the intention-to-treat and per-protocol analysis,the eradication rate was higher in the OST-14 group compared to the QT-10 group:(93.5%,85.5%P=0.04)and(96.2%,89.5%P=0.03)respectively.However,there was no statist-ically significant difference in eradication rates between the OST-14 and QT-14 groups:(93.5%,91.8%P=0.34)and(96.2%,94.4%P=0.35),respectively.The overall incidence of AEs was significantly lower in the OST-14 group(P=0.01).Furthermore,OST-14 was the most cost-effective among the three groups.CONCLUSION The optimized 14-d sequential therapy is a safe and effective alternative.Its eradication rate is comparable to that of the 14-d concomitant therapy while causing fewer AEs and allowing a gain in terms of cost.

Opportunities and challenges of CD47-targeted therapy in cancer immunotherapy

Cancer immunotherapy has emerged as a promising strategy for the treatment of cancer,with the tumor microenvironment(TME)playing a pivotal role in modulating the immune response.CD47,a cell surface protein,has been identified as a crucial regulator of the TME and a potential therapeutic target for cancer therapy.However,the precise functions and implications of CD47 in the TME during immunotherapy for cancer patients remain incompletely understood.This comprehensive review aims to provide an overview of CD47’s multifaced role in TME regulation and immune evasion,elucidating its impact on various types of immunotherapy outcomes,including checkpoint inhibitors and CAR T-cell therapy.Notably,CD47-targeted therapies offer a promising avenue for improving cancer treatment outcomes,especially when combined with other immunotherapeutic approaches.The review also discusses current and potential CD47-targeted therapies being explored for cancer treatment and delves into the associated challenges and opportunities inherent in targeting CD47.Despite the demonstrated effectiveness of CD47-targeted therapies,there are potential problems,including unintended effects on healthy cells,hematological toxicities,and the development if resistance.Consequently,further research efforts are warranted to fully understand the underlying mechanisms of resistance and to optimize CD47-targeted therapies through innovative combination approaches,ultimately improving cancer treatment outcomes.Overall,this comprehensive review highlights the significance of CD47 as a promising target for cancer immunotherapy and provides valuable insight into the challenges and opportunities in developing effective CD47-targeted therapies for cancer treatment.