Precise planning based on 3D-printed dry-laboratory models can reduce perioperative complications of laparoscopic surgery for complex hepatobiliary diseases: a preoperative cohort study.

BACKGROUND & AIMS: Complications after laparoscopic liver resection (LLR) are important factors affecting the prognosis of patients, especially for complex hepatobiliary diseases. The present study aimed to evaluate the value of a three-dimensional (3D) printed dry-laboratory model in the precise planning of LLR for complex hepatobiliary diseases. METHODS: Patients with complex hepatobiliary diseases who underwent LLR were preoperatively enrolled, and divided into two groups according to whether using a 3D-printed dry-laboratory model (3D vs. control group). Clinical variables were assessed and complications were graded by the Clavien-Dindo classification. The Comprehensive Complication Index (CCI) scores were calculated and compared for each patient. Multivariable analysis was performed to determine the risk factors of postoperative complications. RESULTS: Sixty-two patients with complex hepatobiliary diseases underwent the precise planning of LLR. Among them, thirty-one patients acquired the guidance of a 3D-printed dry-laboratory model, and others were only guided by traditional enhanced CT or MRI. The results showed no significant differences between the two groups in baseline characters. However, compared to the control group, the 3D group had a lower incidence of intraoperative blood loss, as well as postoperative 30-day and major complications, especially bile leakage (all P < 0.05). The median score on the CCI was 20.9 (range 8.7-51.8) in the control group and 8.7 (range 8.7-43.4) in the 3D group (mean difference, -12.2, P = 0.004). Multivariable analysis showed the 3D model was an independent protective factor in decreasing postoperative complications. Subgroup analysis also showed that a 3D model could decrease postoperative complications, especially for bile leakage in patients with intrahepatic cholelithiasis. CONCLUSION: The 3D-printed models can help reduce postoperative complications. The 3D-printed models should be recommended for patients with complex hepatobiliary diseases undergoing precise planning LLR.

Survival benefit from adjuvant TACE combined with Lenvatinib for patients with hepatocellular carcinoma and microvascular invasion after curative hepatectomy.

BACKGROUND AND AIMS: The prognosis of patients with hepatocellular carcinoma (HCC) undergoing hepatectomy is unsatisfactory, especially for those with microvascular invasion (MVI). This study aimed to determine the impact of adjuvant transcatheter arterial chemoembolization (TACE) and Lenvatinib on the prognosis of patients with HCC and MVI after hepatectomy. METHODS: Patients diagnosed with HCC and MVI were reviewed, and stratified into four groups according to adjuvant TACE and/or Lenvatinib. Multivariate Cox regression analyses are used to determine independent risk factors. RESULTS: 346 patients were included, and divided into four groups (Group I, TACE+ Lenvatinib; Group II, Lenvatinib; Group III, TACE; Group IV, without adjuvant therapy). Multivariable analysis showed that compared to Group IV, Group I had the best effect on improving the overall survival (OS, HR 0.321, 95%CI 0.099-0.406, P = 0.001) and recurrence-free survival (RFS, HR 0.319, 95%CI 0.129-0.372, P = 0.001). Additionally, compared with Group II or Group III, Group I also can significantly improve the OS and RFS. There is no significant difference between Group II and Group III in OS and RFS. CONCLUSION: The combination of TACE and Lenvatinib should be considered for anti-recurrence therapy for patients with HCC and MVI after hepatectomy.

The role of RASA2 in predicting radioresistance in lung cancer through regulation of p53.

Background: One of the most common causes of lung cancer relapse after clinical treatment is radioresistance. However, the mechanism underlying radioresistance remains unclear. In this study, we investigated the role of Ras p21 protein activator (RASA2) in non-small cell lung cancer (NSCLC). Methods: The messenger RNA (mRNA) of RASA2 was tested via reverse-transcription quantitative polymerase chain reaction (RT-qPCR) of cancer tissues from patients with NSCLC. Computed tomography (CT) and bioluminescent imaging (BLI) were used to monitor the tumor growth of patients and orthotopic mice, respectively. Protein-protein interaction was quantified via immunoprecipitation and glutathione S transferase (GST) pulldown assay. Western blotting was used to evaluate the phosphorylation and ubiquitination level of p53. Results: The results indicated a negative correlation between the mRNA expression levels of RASA2 in tumor tissues with patients' response to radiotherapy. Patients with a high expression of RASA2 had a lower objective response rate (ORR) after 1 month of radiotherapy than patients with low expression of RASA2 after 1 month of radiotherapy. In terms of mechanism, we proved that RASA2 can directly bind to p53 to promote the phosphorylation of p53, which inhibits its transcriptional activity and further promotes its degradation through the ubiquitin/proteasome pathway. In this process, the apoptosis of tumor cells is inhibited due to impaired p53 surveillance, which leads to radioresistance. Conclusions: Our results demonstrate that RASA2 negatively regulates p53 in cancer cells and therefore promotes radioresistance, providing a new predictive biomarker and a potential therapeutic target for radioresistance.

Effect of early peri-operative arterial lactate concentration level ratios on post-hepatectomy liver failure.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after hepatectomy and a major cause of death. The current criteria for PHLF diagnosis (ISGLS consensus) require laboratory data of elevated INR level and hyperbilirubinemia on or after postoperative day 5. This study aims to propose a new indicator for the early clinical prediction of PHLF. METHODS: The peri-operative arterial lactate concentration level ratios were derived from time points within the 3 days before surgery and within POD1, the patients were divided into two groups: high lactate ratio group (≥ 1) and low lactate ratio group (< 1). We compared the differences in morbidity rates between the two groups. Utilized logistic regression analysis to identify the risk factors associated with PHLF development and ROC curves to compare the predictive value of lactate ratio and other liver function indicators for PHLF. RESULTS: A total of 203 patients were enrolled in the study. Overall morbidity and severe morbidity occurred in 64.5 and 12.8 per cent of patients respectively. 39 patients (19.2%) met the criteria for PHLF, including 15 patients (7.4%) with clinically relevant Post-hepatectomy liver failure (CR-PHLF). With a significantly higher incidence of PHLF observed in the lactate ratio ≥ 1 group compared to the lactate ratio < 1 group (n = 34, 26.8% vs. n = 5, 6.6%, P < 0.001). Multivariable logistic regression analysis revealed that a lactate ratio ≥ 1 was an independent predictor for PHLF (OR: 3.239, 95% CI 1.097-9.565, P = 0.033). Additionally, lactate ratio demonstrated good predictive efficacy for PHLF (AUC = 0.792). CONCLUSIONS: Early assessment of peri-operative arterial lactate concentration level ratios may provide experience in early intervention of complications in patients with hepatocellular carcinoma, which can reduce the likelihood of PHLF occurrence and improve patient prognosis.

Targeting pro-inflammatory T cells as a novel therapeutic approach to potentially resolve atherosclerosis in humans.

Atherosclerosis (AS), a leading cause of cardio-cerebrovascular disease worldwide, is driven by the accumulation of lipid contents and chronic inflammation. Traditional strategies primarily focus on lipid reduction to control AS progression, leaving residual inflammatory risks for major adverse cardiovascular events (MACEs). While anti-inflammatory therapies targeting innate immunity have reduced MACEs, many patients continue to face significant risks. Another key component in AS progression is adaptive immunity, but its potential role in preventing AS remains unclear. To investigate this, we conducted a retrospective cohort study on tumor patients with AS plaques. We found that anti-programmed cell death protein 1 (PD-1) monoclonal antibody (mAb) significantly reduces AS plaque size. With multi-omics single-cell analyses, we comprehensively characterized AS plaque-specific PD-1+ T cells, which are activated and pro-inflammatory. We demonstrated that anti-PD-1 mAb, when captured by myeloid-expressed Fc gamma receptors (FcγRs), interacts with PD-1 expressed on T cells. This interaction turns the anti-PD-1 mAb into a substitute PD-1 ligand, suppressing T-cell functions in the PD-1 ligands-deficient context of AS plaques. Further, we conducted a prospective cohort study on tumor patients treated with anti-PD-1 mAb with or without Fc-binding capability. Our analysis shows that anti-PD-1 mAb with Fc-binding capability effectively reduces AS plaque size, while anti-PD-1 mAb without Fc-binding capability does not. Our work suggests that T cell-targeting immunotherapy can be an effective strategy to resolve AS in humans.

TyG-GGT is a Reliable Non-Invasive Predictor of Advanced Liver Fibrosis in Overweight or Obese Individuals.

BACKGROUND: Liver fibrosis is a predisposing factor for liver cancer. This study will investigate the predictive role of the Triglyceride-glucose and Gamma-glutamyl transferase index (TyG-GGT) as a non-invasive indicator of advanced liver fibrosis in individuals with obesity or overweight. METHOD: We enrolled patients who underwent metabolic and bariatric surgery as well as intraoperative liver biopsies at Zhejiang provincial people's hospital from August 2020 to March 2023. Clinical characteristics, comorbidities, laboratory data, and pathological variables of patients were collected and analysed. Then, we conducted logistics regression model to compare the performance of the TyG-GGT index with other 4 non-invasive models. RESULTS: A total of 65 patients were included in this study. 43(66.2%) of them were female, with the mean body mass index (BMI) of 39.0 ± 7.3 kg/m2. Meanwhile, 24(36.9%) patients were diagnosed with diabetes. Advanced liver fibrosis were observed in 16.9% of patients, while liver cirrhosis was found in 4.6% of patients. The multivariable logistics regression showed that TyG-GGT was an independent risk factor of advanced liver fibrosis (OR = 6.989, P = 0.049). Additionally, compared to another 4 non-invasive liver fibrosis models (NFS = 0.66, FIB4 = 0.65, METS-IR = 0.68, APRI = 0.65), TyG-GGT exhibits the highest AUC value of 0.75. CONCLUSIONS: More than one-third of patients undergoing metabolic and bariatric surgery are afflicted with nonalcoholic steatohepatitis (NASH), and a significant proportion exhibit advanced fibrosis. TyG-GGT was a potentially reliable predictor for screening individuals with overweight or obesity at high risk of advanced liver fibrosis, thus providing clinical guidance for early intervention in this targeted group.

Endoscopic retrograde appendicitis treatment for periappendiceal abscess: A case report.

BACKGROUND: Acute appendicitis is the most common abdominal emergency. At present, the main treatments for periappendiceal abscess include antibiotics and surgery. However, the complications and mortality of emergency surgery are high. The preferred therapy is conservative treatment with antibiotics first, ultrasound-guided puncture drainage or surgical treatment is followed when necessary. Endoscopic retrograde appendicitis therapy (ERAT) for acute uncomplicated appendicitis have been proved clinically effective, but it is rarely used in periappendiceal abscess. CASE SUMMARY: We report a patient admitted to hospital because of "right lower abdominal pain for six days". The computerized tomography (CT) of patient showed that appendicitis with fecaliths and abscess in the pelvis. The patient was treated by CT-guided puncture and drainage of abdominal abscess combined with ERAT to remove appendiceal fecaliths, irrigation and stent placement. CONCLUSION: The patient did not receive surgery because of impoverished family. Abdominal pain did not recur during the follow-up period. This case confirms the value of ERAT in the treatment of periappendiceal abscess.

Automatic origin prediction of liver metastases via hierarchical artificial-intelligence system trained on multiphasic CT data: a retrospective, multicentre study.

Background: Currently, the diagnostic testing for the primary origin of liver metastases (LMs) can be laborious, complicating clinical decision-making. Directly classifying the primary origin of LMs at computed tomography (CT) images has proven to be challenging, despite its potential to streamline the entire diagnostic workflow. Methods: We developed ALMSS, an artificial intelligence (AI)-based LMs screening system, to provide automated liver contrast-enhanced CT analysis for distinguishing LMs from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), as well as subtyping primary origin of LMs as six organ systems. We processed a CECT dataset between January 1, 2013 and June 30, 2022 (n = 3105: 840 HCC, 354 ICC, and 1911 LMs) for training and internally testing ALMSS, and two additional cohorts (n = 622) for external validation of its diagnostic performance. The performance of radiologists with and without the assistance of ALMSS in diagnosing and subtyping LMs was assessed. Findings: ALMSS achieved average area under the curve (AUC) of 0.917 (95% confidence interval [CI]: 0.899-0.931) and 0.923 (95% [CI]: 0.905-0.937) for differentiating LMs, HCC and ICC on both the internal testing set and external testing set, outperformed that of two radiologists. Moreover, ALMSS yielded average AUC of 0.815 (95% [CI]: 0.794-0.836) and 0.818 (95% [CI]: 0.790-0.842) for predicting six primary origins on both two testing sets. Interestingly, ALMSS assigned origin diagnoses for LMs with pathological phenotypes beyond the training categories with average AUC of 0.761 (95% [CI]: 0.657-0.842), which verify the model's diagnostic expandability. Interpretation: Our study established an AI-based diagnostic system that effectively identifies and characterizes LMs directly from multiphasic CT images. Funding: National Natural Science Foundation of China, Guangdong Provincial Key Laboratory of Medical Image Processing.

Multifunctional ZnO@DOX/ICG-LMHP Nanoparticles for Synergistic Multimodal Antitumor Activity.

Multifunctional nanoparticles are of significant importance for synergistic multimodal antitumor activity. Herein, zinc oxide (ZnO) was used as pH-sensitive nanoparticles for loading the chemotherapy agent doxorubicin (DOX) and the photosensitizer agent indocyanine green (ICG), and biocompatible low-molecular-weight heparin (LMHP) was used as the gatekeepers for synergistic photothermal therapy/photodynamic therapy/chemotherapy/immunotherapy. ZnO was decomposed into cytotoxic Zn2+ ions, leading to a tumor-specific release of ICG and DOX. ZnO simultaneously produced oxygen (O2) and reactive oxygen species (ROS) for photodynamic therapy (PDT). The released ICG under laser irradiation produced ROS for PDT and raised the tumor temperature for photothermal therapy (PTT). The released DOX directly caused tumor cell death for chemotherapy. Both DOX and ICG also induced immunogenic cell death (ICD) for immunotherapy. The in vivo and in vitro results presented a superior inhibition of tumor progression, metastasis and recurrence. Therefore, this study could provide an efficient approach for designing multifunctional nanoparticles for synergistic multimodal antitumor therapy.

Lithium carbonate revitalizes tumor-reactive CD8+ T cells by shunting lactic acid into mitochondria.

The steady flow of lactic acid (LA) from tumor cells to the extracellular space via the monocarboxylate transporter symport system suppresses antitumor T cell immunity. However, LA is a natural energy metabolite that can be oxidized in the mitochondria and could potentially stimulate T cells. Here we show that the lactate-lowering mood stabilizer lithium carbonate (LC) can inhibit LA-mediated CD8+ T cell immunosuppression. Cytoplasmic LA increased the pumping of protons into lysosomes. LC interfered with vacuolar ATPase to block lysosomal acidification and rescue lysosomal diacylglycerol-PKCθ signaling to facilitate monocarboxylate transporter 1 localization to mitochondrial membranes, thus transporting LA into the mitochondria as an energy source for CD8+ T cells. These findings indicate that targeting LA metabolism using LC could support cancer immunotherapy.

Immunotherapeutic prospects and progress in bladder cancer.

Bladder cancer is one of the most common malignant tumours of the urogenital system, with high morbidity and mortality. In most cases, surgery is considered the first choice of treatment, followed by adjuvant chemotherapy. However, the 5-year recurrence rate is still as high as 65% in patients with non-invasive or in situ tumours and up to 73% in patients with slightly more advanced disease at initial diagnosis. Various treatment methods for bladder cancer have been developed, and hundreds of new immunotherapies are being tested. To date, only a small percentage of people have had success with new treatments, though studies have suggested that the combination of immunotherapy with other therapies improves treatment efficiency and positive outcomes for individuals, with great hopes for the future. In this article, we summarize the origins, therapeutic mechanisms and current status of research on immunotherapeutic agents for bladder cancer.

Sagittal septum duplication of bladder and duplication of posterior urethra combined with congenital megacolon: a case report and literature review.

BACKGROUND: Duplication of the bladder with duplication of the posterior urethra is a relatively rare congenital malformation. Cases of sagittal septum duplication of the bladder with duplication of the posterior urethra have rarely been reported. Furthermore, the combination thereof with congenital megacolon is rare. CASE PRESENTATION: A 21-year-old male was admitted to our hospital because of frequent urination for two months. He presented to another hospital first with frequent urination and underwent computed tomography (CT) and testicular biopsy. Anti-inflammatory therapy was administered by the doctor to the patient. For further diagnosis and treatment, the patient went to the outpatient department in our hospital on June 6, 2022. After admission, the patient underwent ultrasound, CT, MRI, cystoscopy, and other related examinations and tests. The examination results suggested that the patient had duplication of the bladder with duplication of the posterior urethra. In addition, the patient's mother reported that he had suffered from long-term constipation with abdominal distension before the age of 5 years. At the time, he was admitted to the local hospital and was diagnosed with congenital megacolon based on the relevant examinations. After the patient was diagnosed with duplication of bladder and urethra, the doctor recommended surgical treatment to the patient. However, he considered that he only had frequent urination symptoms, and chose conservative treatment rather than to undergo surgical treatment. Thus, the doctor prescribed anti-inflammatory treatment. Four months later, the patient reported that frequent urination symptoms persisted, and was also considering fertility-related problems. The outpatient follow-up will be continued. CONCLUSIONS: In this article, we summarize the imaging findings of duplication of the bladder with duplication of the posterior urethra and propose the advantages and disadvantages of each type of imaging examination. We also review the relevant literature on cases of bladders with duplication of the posterior urethra. The related differential diagnosis is summarized, and the significance of guiding clinical treatment and diagnosis is discussed.

5-methylcytosine-mediated upregulation of circular RNA 0102913 augments malignant properties of colorectal cancer cells through a microRNA-571/Rac family small GTPase 2 axis.

Circular RNAs (circRNAs) are a class of stable non-coding RNAs that have emerged as key regulators in human diseases including cancer. This study investigates the role of circRNA_0102913 (circ_0102913) in malignant behavior of colorectal cancer (CRC) cells and the underpinning mechanisms. By analyzing CRC-related GSE197991, GSE159669, and GSE223001 datasets, we obtained circ_0102913 as an aberrantly upregulated circRNA in CRC. Increased circ_0102913 expression was detected in CRC tissues and cells. By querying multiple bioinformatics systems (circBank, Circular RNA Interactome, TargetScan, miRDIP, miRwalk, and miRDB), we identified microRNA-571 (miR-571) as a target of circ_0102913 and Rac family small GTPase 2 (RAC2) mRNA as a target of miR-571. Biotinylated-RNA pull-down and/or luciferase assays showed that circ_0102913 bound to miR-571 to restore the expression of RAC2 mRNA. Circ_0102913 silencing or miR-571 overexpression repressed proliferation, migration and invasion, and in vivo tumorigenesis abilities of CRC cells. However, the malignant properties of cells were restored by RAC2 overexpression. The increased circ_0102913 expression in CRC cells was attributed to increased 5-methylcytosine (m5C) modification levels. Silencing of NOP2/Sun RNA methyltransferase 5 reduced the m5C level and therefore reduced stability and expression of circ_0102913 expression in CRC cells. In conclusion, this study demonstrates that m5C-mediated upregulation of circ_0102913 augments malignant properties of CRC cells through a miR-571/RAC2 axis.

The creation and validation of predictive models to assess the risk of unfavorable outcomes following hybrid total arch repair for Stanford type A aortic dissection.

BACKGROUND: The objective of this study was to develop and validate a nomogram for the individualized prediction of adverse events in patients with Stanford type A aortic dissection (TAAD) undergoing hybrid total aortic arch repair. METHODS: From April 2019 to April 2022, we conducted a comprehensive review of the medical records of Stanford type A aortic dissection patients who underwent hybrid total aortic arch repair surgery at our hospital. Patients were separated into two groups based on whether or not a composite adverse event occurred following surgery. Using univariate and multivariate analyses of logistic regression, the prediction model was created. Construct risk prediction models utilizing nomograms and evaluate their precision, discrimination, and clinical utility. RESULTS: Age, platelets, serum blood urea nitrogen, and ascending aortic diameter were the variables included in the nomogram by univariate and multivariate analysis. The risk model performed well in internal validation, with an area under the curve (AUC) of 0.829. The calibration curve demonstrated good agreement between predicted and actual probabilities (Hosmer-Lemeshow test, P = 0.22). Clinical decision analysis curves demonstrate predictive nomograms' clinical utility. CONCLUSION: This study created and validated a nomogram for predicting the risk of composite endpoint events in TAAD patients undergoing hybrid total aortic arch repair. The nomogram can help determine the severity of a patient's condition and provide a more personalized diagnosis and treatment.

Prognostic value of platelet distribution width to lymphocyte ratio in patients with hepatocellular carcinoma following hepatectomy.

BACKGROUND: Platelet distribution width (PDW), but not platelet count, was found to more comprehensively reflect platelet activity. The present study, thus, aimed to evaluate the prognostic value of PDW to lymphocyte ratio (PDWLR) in patients with hepatocellular carcinoma (HCC) following hepatectomy. METHODS: Patients following hepatectomy were analyzed retrospectively. The Kaplan-Meier survival curves and Cox regression model were used to determine the prognostic value of PDWLR. RESULTS: 241 patients were analyzed eventually, and stratified into low and high PDWLR groups (≤ 9.66 vs. > 9.66). Results of comparing the baseline characteristics showed that high PDWLR was significantly associated with cirrhosis, and intraoperative blood loss (all P < 0.05). In multivariate COX regression analysis, PDWLR was demonstrated as an independent risk factor for OS (HR: 1.549, P = 0.041) and RFS (HR: 1.655, P = 0.005). Moreover, PDWLR demonstrated a superior capacity for predicting prognosis compared to other indicators. CONCLUSION: Preoperative PDWLR has a potential value in predicting the prognosis of HCC patients following hepatectomy, which may help in clinical decision-making for individual treatment.

Neoadjuvant Lorlatinib Induces Pathological Complete Response in Advanced ALK-Positive Lung Cancer: A Case Report.

BACKGROUND Chemotherapy has been the conventional treatment method for advanced non-small-cell lung cancer (NSCLC). Nevertheless, the identification and comprehension of oncogenic driver alterations have paved the way for targeted therapies, significantly enhancing patient outcomes. The management of locally advanced NSCLC that is positive for ALK presents a challenge due to the lack of reported randomized controlled trials. The efficacy of neoadjuvant and adjuvant targeted therapy in this context remains uncertain. CASE REPORT A 54-year-old man was diagnosed with stage IIIB (pT1N3M0) upper right lung adenocarcinoma carrying the EML4-ALK fusion gene. Clinically, the patient had multiple enlarged lymph nodes in the right hilum and mediastinum, with the largest measuring approximately 28×19 mm by CT scan and we found that the L4 lymph node was invaded by metastasis. Then, the patient received 1 cycle of chemotherapy with paclitaxel in combination with nedaplatin and subsequently received maintenance treatment involving lorlatinib. Two months later, clinical evaluations revealed progressive reduction of the lesions, especially the reduced size of the mediastinal lymph nodes. Therefore, the patient underwent thoracoscopic partial lobectomy and lymphadenectomy and achieved pathological complete response (pCR). After 3 months, a follow-up CT scan was similar to the first postoperative CT scan and no tumor was found. CONCLUSIONS This case demonstrates the potential advantage of lorlatinib as a neoadjuvant therapy in advanced ALK-positive NSCLC. It emphasizes the importance of identifying new therapeutic targets by next-generation sequencing (NGS) and implementing precise treatment strategies in clinical practice.

Naples Prognostic Score is an Independent Prognostic Factor in Patients Undergoing Hepatectomy for Hepatocellular Carcinoma.

Background: Nutritional and inflammatory status has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC), but many studies did not include all biomarkers simultaneously. The present study aimed to determine the impact of Naples prognostic score (NPS) on the long-term survival in patients undergoing hepatectomy for HCC. Methods: Patients with HCC after curative resection were eligible. Then, all patients were stratified into three groups according to the NPS. Clinical features and survival outcomes were compared among the three groups. Independent prognostic factors were determined by COX analysis. The time dependent receiver operating characteristic (ROC) curves were used to compare prognostic performance with other immunonutrition scoring systems. Results: A total of 476 patients were enrolled eventually. Baseline characteristics showed that patients with higher NPS had a higher proportion of poor liver function and advanced tumor features. Accordingly, Kaplan-Meier survival curves showed that patients with higher NPS had a lower rate of overall survival (OS) and recurrence-free survival (RFS). Multivariable COX analysis demonstrated that NPS was an independent risk factor of OS (NPS group 2 vs 1: HR=1.958, 95% CI: 1.038-3.369, p = 0.038; NPS group 3 vs 1: HR=2.608, 95% CI: 1.358-5.008, p=0.004, respectively) and RFS (NPS group 2 vs 1: HR=2.014, 95% CI: 1.299-2-3.124, p=0.002; NPS group 3 vs 1: HR=2.002, 95% CI: 1.262-3.175, p=0.003, respectively). The time-dependent ROC curve showed that NPS was superior to other models in prognostic performance and discriminatory power for long-term survival (median AUC 0.675, 95% CI: 0.586-0.712, P < 0.05). Conclusion: The NPS is a simple tool strongly associated with long-term survival in patients undergoing curative hepatectomy for HCC.

BATF2 inhibits PD-L1 expression and regulates CD8+ T-cell infiltration in non-small cell lung cancer.

Immune checkpoint blockades have made huge breakthrough among some cancer types including lung cancer. However, only a small proportion of patients will benefit from immune checkpoint blockades; other patients have no or minor response to immunotherapy. The underlying mechanisms and efficient biomarkers to predict immunotherapy resistances remain unclear and lacking. In this study, BATF2 knockout mice, human xenograft mice, were used for in vivo studies. Relevant RNA and protein levels were analyzed by RT-quantitative PCR and Western blotting. As a result, we found that the expression of BATF2 is negatively correlated with expression of programmed death-ligand 1 in the plasma of patients. Mechanically, we showed that BATF2 inhibits programmed death-ligand 1 expression in cancer cells by inhibiting the PI3K-AKT pathway where ZEB2 plays an important role in this process. Based on bioinformatics analysis, we found that the function of BATF2 in promoting antitumor immune response in patients with non-small cell lung cancer, which is mediated by BATF2, enhances CD8+ T-cell infiltration as well as activation. The expression of BATF2 from circulating tumor cells and tissues can be serve as an efficient biomarker to predict diagnosis, prognosis, and immunotherapy efficacy.

Single-cell analysis reveals HBV-specific PD-1+CD8+ TRM cells in tumor borders are associated with HBV-related hepatic damage and fibrosis in HCC patients.

Immune checkpoint blockade (ICB) treatment of hepatocellular carcinoma (HCC) patients with hepatitis B virus (HBV) infection may activate viral-specific T cells to attack HBV infected hepatocytes and thus induce immune-related liver injury. Therefore, it is important to deeply understand the impacts of HBV infection on HCC immune microenvironment in order to better design effective immunotherapies for HBV+ (HBV infected) HCC patients. Here, We performed cytometry by time-of-flight (CyTOF) analyses to characterize the distinct immune compositions of HCC tumors, tumor borders, and their associations with HCC/HBV related clinical characteristics. We identified 31 distinct immune clusters and found significant associations between immune signatures with clinicopathological features of HCC. We further revealed the HBV infection had more effects on shaping immune compositions in tumor borders than in tumors, with the significant enrichment of HBV-specific PD-1+CD8+ tissue-resident memory T (TRM) cells in tumor borders of HBV+ patients. We confirmed this subset with a more exhausted phenotype and respond more actively under anti-PD-L1 treatment, suggesting its involvement in immune-related liver injury induced by ICB treatment to HBV+ HCC patients. Our study shows it may be necessary to consider antiviral prophylaxis for HBV+ HCC patients receiving ICB treatment.