Conventional inflammatory bowel disease therapies are limited by inefficient colon-targeted delivery, systemic side effects, and a failure to rectify the underlying oxidative stress and immune dysregulation. Riboflavin (RAF) possesses ideal antioxidant and immunomodulatory properties for colitis therapy but suffers from rapid proximal absorption. While acid-degradable metal-organic framework (MOF) nanozymes can co-deliver RAF and catalytically eliminate reactive oxygen species (ROS), they lack colon-retentive capacity. To overcome these barriers, we engineered an acid-enhanced, drinkable hydrogel for the coordinated delivery of riboflavin-loaded Pt-MOF nanozymes (RAF@Pt-ZIF@CS, RPZCS). This food-grade sodium alginate system undergoes a drinkable sol-to-mucoadhesive gel transition triggered specifically by the acidic colonic microenvironment (pH 5.0–6.0). The subsequent acid-etching of the Pt-MOF framework enables spatiotemporally coupled burst release of RAF and Pt ions. In a DSS-induced colitis model, RPZCS demonstrated superior lesion retention and exerted comprehensive therapeutic effects. It robustly scavenged ROS via the SCAD-DJ-1–KEAP1–Nrf2 pathway, suppressed pro-inflammatory M1 macrophage polarization, rebalanced the Treg/Th17 immune axis and pro-/anti-inflammatory cytokines, enhanced mucosal/epithelial barrier integrity and restore gut microbiota. Furthermore, RPZCS favorably remodeled the gut microbiota structure. A 14-day repeated-dose toxicity study confirmed its “drinkable-grade” safety. Collectively, this acid-responsive hydrogel platform achieves orchestrated inflammation-immune modulation and redox homeostasis, offering a safe, effective, and highly compliant oral strategy for targeted colitis therapy.

Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) colorectal cancer, offering durable clinical benefits to a subset of patients. However, long-term survival is heterogeneous, and effective risk-stratification biomarkers for this subgroup are needed. This study investigated the prognostic significance of baseline serum uric acid (UA) levels in patients with dMMR/MSI-H colorectal cancer undergoing ICI therapy. This retrospective study enrolled 171 patients with advanced dMMR/MSI-H colorectal cancer receiving ICIs (monotherapy or combined with chemotherapy/targeted agents). Serum UA was measured within three days pre-treatment. An optimal UA cut-off was determined by receiver operating characteristic (ROC) curve analysis. Kaplan-Meier estimates and Cox proportional hazards models assessed the UA-overall survival (OS) association. Median follow-up was 21.1 months (range: 1.2–48.0). ROC analysis identified an optimal serum UA threshold of 274 µmol/L (Area Under Curve (AUC) = 0.82; sensitivity = 70.0

8580 Background: Despite advancements in first-line treatments such as immunotherapy and targeted therapies, resistance to these treatments is common, especially those IO-treated and low PD-L1 TPS, creating a significant unmet need for effective second-line therapies. IMM2510 is a bispecific fusion protein targeting PD-L1 and VEGF which can modify tumor microenvironment to overcome resistance and improve sensibility to antitumor agents. The data of dose-escalation phase I was previously reported in ASCO2024. Here we summarize the updated efficacy and safety results of IMM2510 in advanced IO-treated SQ-NSCLC. Part of the data were previously reported in WCLC 2025. Methods: The phase I study was designed as a first-in-human, open-label, multi-center study to evaluate the safety, efficacy, PK and PD of IMM2510 in pts with advanced solid tumors. Eligible pts were enrolled to receive IMM2510 via intravenous infusion Q2W. Results: As of 31 Dec 2025, 32 pts with advanced IO-treated SQ-NSCLC received IMM2510. The median age was 61 years; 31.3% pts had PD-L1 TPS < 1%; 75.0% pts had ECOG score of 1; the median prior lines of anti-tumor therapy were 2 (range: 1-5). All 32 pts experienced TEAEs. Grade ≥3 TEAEs were reported by 17 (53.1%) pts; Grade ≥3 TRAEs were reported by 12 (37.5%) pts; TRAEs leading to treatment discontinuation were reported by 1 (3.1%) participant. No participant experienced TRAE leading to death. 22 pts with advanced IO-treated SQ-NSCLC were evaluable for efficacy analysis. The ORR was 27.3% (6/22) and DCR was 81.8% (18/22). The median DoR was 11.1 months. The median PFS was 9.4 months at the median follow-up time of 8.3 months. The median overall survival was not reached. Exposure-response (ER) analysis within the 3 - 20 mg/kg dose range revealed a positive exposure-efficacy relationship in pts with SQ-NSCLC, with higher exposure corresponding to increased ORR or DCR, while a relatively flat ER was observed for Grade 3 or higher TRAE and most common AEs in NSCLC. Thus, 20 mg/kg Q2W was selected as the RP2D with well-balanced efficacy-safety profiles. Conclusions: In pts with advanced IO-treated SQ-NSCLC, IMM2510 provides clinical meaningful benefit and supports a favorable benefit-risk profile. The phase III clinical study is being planned. Clinical trial information: NCT05972460 .

The disruption of the intestinal mucosal barrier is strongly associated with the onset of various diseases, including inflammatory bowel disease. Exopolysaccharides (EPS) support the functionality of the intestinal barrier. Weissella Cibaria (W. cibaria), belonging to the lactic acid bacteria, exhibits a significant capacity for EPS production. However, the specific mechanisms by which the EPS produced by W. cibaria confers intestinal barrier protection remain unexplored. Here, we characterized the polysaccharide, EPS-2, produced by W. cibaria isolated from the feces of healthy infants. EPS-2 was a novel dextran composed of α-(1 → 6) and α-(1 → 3,6) glycosidic linkages with a molecular weight of 845 kDa. EPS-2 alleviates intestinal mucosal barrier dysfunction in a mouse model of colitis, via a mechanism specifically reliant on the gut microbiota and their metabolic products, which is different from the well-known direct protective effects of other EPS on the intestinal barrier. EPS-2 reversed colitis-induced reductions in Muribaculaceae and propionate levels, thereby enhancing colonic goblet cell function and mucin content. Additionally, EPS-2 decreased the number of LPS-producing bacteria, such as Escherichia_Shigella. EPS-2 alleviated dextran sulfate sodium-induced intestinal inflammation and barrier damage. Therefore, EPS-2 shows promise as a postbiotic treatment for diseases associated with intestinal barrier dysfunction.

Lung cancer frequently metastasizes to the brain, posing significant therapeutic challenges. To address this, we developed HLP@SiTGF-β1, a hybrid biomimetic nanoparticle integrating phototherapy, gene silencing, and immunotherapy. The system comprises a ZIF-8 core loaded with TGF-β1-targeting siRNA (SiTGF-β1), enveloped by a hybrid membrane fusing liposomes (loading the phototherapeutic agent IR-780) with Lewis lung carcinoma (LLC) cell membranes. This design enables homologous tumor targeting, prolonged circulation, and immune evasion. In vitro and in vivo studies demonstrated that near-infrared (NIR) irradiation triggers immunogenic cell death (ICD) via photodynamic (PDT) and photothermal (PTT) effects, while siRNA-mediated TGF-β1 knockdown alleviates tumor hypoxia, enhances PDT efficacy, reduces regulatory T cell (Treg) differentiation, and promotes cytotoxic CD8+T cell infiltration. The nanoparticles efficiently penetrated the blood–brain barrier in a brain metastasis model, significantly suppressing intracranial tumor growth under NIR light. This “four-in-one” strategy—combining PDT, PTT, gene therapy, and immunotherapy—offers a promising multimodal platform for treating lung cancer and its brain metastases.

Background Esophageal cancer (EC) is the seventh most prevalent cancer and the sixth most common cause of cancer-related mortalities worldwide. Camrelizumab, a monoclonal antibody, has demonstrated moderate efficacy in esophageal squamous cell carcinoma (ESCC). Lactobacillus paracasei, a probiotic bacterium, has a complementary effect in immunotherapy. This study aimed to evaluate the combination of camrelizumab and L. paracasei for advanced ESCC. Methods This single-arm, single-center, exploratory trial was conducted at the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China. Eligible patients received 200 mg camrelizumab biweekly and two bags of L. paracasei twice daily. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were disease control rate (DCR), overall survival (OS), objective response rate (ORR), and adverse events (AEs). Results From May 2020 to October 2022, ten patients with advanced ESCC who did not respond to first-line therapy were admitted. At the data cutoff date (August 9, 2023), the median follow-up duration was 12 months. Two of 10 (20%) achieved objective responses. The median survival was 7.5 months and the median OS was not reached. Grade 3 treatment-related AEs occurred in two of the 10 patients (20%). No serious treatment-related AEs or deaths occurred. Conclusions Camrelizumab combined with L. paracasei showed favorable anticancer activity and may be a viable second-line treatment for patients with ESCC.Trial registration: ChiCTR2000032093, https://www.chictr.org.cn.

Lipid degradation is generally considered an antagonistic pathway to lipid synthesis, so this pathway is often removed to improve lipid production. In this study, triacylglycerol (TAG) cycling formed by lipid degradation is found to be crucial for long-chain polyunsaturated fatty acid (PUFA) biosynthesis; this result contradicts the notion that lipid degradation is a useless process. Specifically, we demonstrate that TAG cycling promoting PUFA biosynthesis occurred in Yarrowia lipolytica and Mortierella alpina via the desaturase/elongase pathway but not in Schizochytrium sp. with the polyketide synthase (PKS) pathway. Exploiting the TAG cycling mechanism, a strategy of decoupling the TAG biosynthesis and degradation is developed. Using this strategy, the titers of C20:5, C22:5 and prostaglandin F2α (PGF2α) in Y. lipolytica are improved by 116.2%, 99.4% and 41.7%, respectively. Our findings highlight the potential of the TAG cycling for related biochemical synthesis in the construction of excellent oleaginous engineered strains.

Purpose:This study aimed to evaluate the nutritional, immune, and inflammatory status of esophageal squamous cell carcinoma (ESCC) patients before immunotherapy using blood-based biomarkers, and to develop and validate competing-risk nomogram models to predict overall survival (OS) and progression-free survival (PFS). Patients and Methods:This retrospective study enrolled 300 ESCC patients who received immunotherapy at the First Affiliated Hospital of Zhengzhou University between January 2021 and December 2023, and randomly assigned them to a primary cohort (210 cases) and a validation cohort (90 cases) at a 7:3 ratio. We screened prognostic factors using least absolute shrinkage and selection operator (LASSO) regression coupled with univariate and multivariate Cox regression analyses to construct a nomogram prediction model. Model validation was performed using the following approaches: (1) Calibration curves were employed to evaluate the agreement between predicted and observed outcomes; (2) Discrimination was assessed through the index of concordance (C-index), time-dependent receiver operating characteristic (ROC) curves, and time-dependent area under the curve (AUC); (3) Clinical utility and predictive accuracy were further assessed using net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA). Furthermore, the performance of the proposed nomogram was systematically compared with the conventional tumor-node-metastasis (TNM) staging system and another published prediction model. Results:Through comprehensive multivariate OS analysis conducted in the primary cohort, we established an innovative prognostic nomogram combining systemic immunoinflammatory index (SII) and prognostic nutritional index (PNI). Compared with TNM staging, our model demonstrated strong accuracy, discriminative ability, and clinical utility in the primary and validation cohorts. Conclusion:This research confirms the prognostic value of SII and PNI in ESCC patients undergoing anti-PD-1 immunotherapy. Given their significant correlation with clinical outcomes, these biomarkers show potential for pretreatment risk assessment in immunotherapy candidates.

11545 Background: IMM2510 is a novel bispecific antibody fusion protein targeting PD-L1 and VEGF. The results of dose-escalation phase were previously reported. Here, we report further efficacy and safety of soft tissue sarcoma patients in cohort expansion stage. Methods: IMM2510-01 was a phase I, multicenter, open-label study designed to evaluate the safety, efficacy, recommended phase II dose (RP2D), and pharmacokinetics (PK) of IMM2510 monotherapy (NCT05972460). Dose escalation stage completed and administration of IMM2510 at 20mg/kg, Q2W was selected for cohort expansion. Advanced soft tissue sarcoma patients after prior systemic treatment failure were enrolled, including these with alveolar soft part sarcoma (ASPS), undifferentiated pleomorphic sarcoma (UPS), leiomyosarcoma (LMS) and synovial sarcoma (SS) patients. The primary endpoint was safety, tolerability and investigator assessed ORR. Results: As of 24 Dec 2024, 29 STS patients were treated in cohort expansion stage, including 10 with ASPS, 5 with UPS, 8 with LMS, 5 with SS and 1 with other STS subtypes. The median age was 45 and most patients (89.7%) were ECOG PS 1. The median number of prior systemic treatment was 2. Most patients (96.6%) experienced treatment-related adverse events (TRAEs), of which 3 (10.3%) were ≥ Grade 3. The most common TRAEs of any grade was infusion-related reaction (IRR) (37.9%), platelet decreased (31%) and AST increased (27.6%). TRAE of ≥ Grade 3 was reported in 3 patients, including 1 platelet decreased, 1 transaminase increased and 1 hypoaesthesia. No TRAE leading to treatment discontinuation was observed. Of 27 efficacy-evaluable STS patients, ORR was 7.4% and DCR was 55.6%. 2 PR and 4 SD with tumor shrinkage were observed. PRs were noted in the UPS and LMS cohorts, with an ORR of 20% and 14.3%, and a DCR of 60% and 42.9%, respectively. The DOR was not reached in UPS and 3.68 months in LMS. The study is ongoing. Conclusions: IMM2510 monotherapy demonstrated active anti-tumor activity in R/R STS patients with tolerable toxicity. Clinical trial information: NCT05972460 .

The clinical utility of doxorubicin (Dox) is limited by severe dose-dependent cardiotoxicity. The disruption of the gut microbiota and mucosal barrier by Dox elevates the levels of circulating lipopolysaccharides (LPS), indicative of low-grade endotoxemia, and contributes to Dox-induced cardiotoxicity (DIC). Exopolysaccharides (EPS) are known to function as postbiotics that can regulate both gut microbiota and mucosal barrier function. However, their ability to mitigate DIC and the underlying mechanisms remain unknown. Hence, this study investigated whether a purified, structurally defined dextran EPS-2, derived from Weissella cibaria, alleviated DIC by restoring intestinal barrier integrity and correcting gut microbiota dysbiosis. Specifically, EPS-2 reduced low-grade endotoxemia by decreasing Dox-elevated Escherichia-Shigella (a major LPS producer positively correlated with cardiac damage), likely by directly inhibiting the proliferation of bacteria belonging to Escherichia-Shigella. Consequently, EPS-2 weakened the dysregulation of cardiac inflammation and oxidative stress. The findings demonstrate that modulating the gut microenvironment with bacterial EPS to reduce low-grade endotoxemia is a promising strategy for preventing chemotherapy-induced cardiotoxicity.

Reactive oxygen species (ROS) have been widely studied for cancer therapy. Nevertheless, instability and aspecific damages to cellular biomolecules limit the application effect. Recently, significant research efforts have been witnessed in the flourishing area of metal nanoclusters (NCs) with atomically precise structures for targeted release of ROS but few achieved success towards targeting tumor microenvironment. In this work, we reported an atomically precise nanocluster Cu6(C4H3N2S)6 (Cu6NC), which could slowly break and generate ROS once encountered with acidic. The as-prepared Cu6NC demonstrated high biological safety and efficient chemodynamic anti-tumor properties. Moreover, Cu6NC enabled transient release of ROS and contained targeting behavior led by the tumor microenvironment. Both in vitro and in vivo experiments confirmed that Cu6NC demonstrated a low cytotoxicity for normal cells, while presented high cytotoxicity for tumor cells with a concentration-dependent manner. This work not only reported a promising candidate for chemodynamic cancer therapy, but also paved the route to address clinical issues at the atomic level.

BackgroundMicrosatellite instability-high (MSI-H) colorectal cancer (CRC) is known for its heightened responsiveness to immunotherapy. However, establishing robust predictive markers for immunotherapy efficacy remains imperative. This retrospective study aimed to elucidate the genetic landscape of MSI-H CRC and correlate these genetic alterations with immunotherapy outcomes in a cohort of 121 patients.MethodsWe analyzed clinical and molecular data from 121 patients with MSI-H CRC. We conducted a thorough genetic analysis of MSI-H CRC patients, with a specific emphasis on the APC, TP53, RAS, and MMR genes. We further analyzed the relationship between gene mutations and immunotherapy efficacy. The primary endpoints analyzed were objective response rate (ORR) and progression-free survival (PFS). All statistical analysis was conducted using SPSS26.0 and R 4.2.0 software.ResultsOur findings underscored the complexity of the genetic landscape in MSI-H CRC, shedding light on the intricate interplay of these genes in CRC development. Notably, mutations in MMR genes exhibited a distinctive pattern, providing insights into the underlying mechanisms of MSI-H. Furthermore, our results revealed correlations between specific genetic alterations and immunotherapy outcomes, with a particular focus on treatment response rates and progression-free survival.ConclusionThis study represents a significant step toward unraveling the genetic nuances of MSI-H CRC. The distinctive pattern of MMR gene mutations not only adds depth to our understanding of MSI-H CRC but also hints at potential avenues for targeted therapies. This research sets the stage for future investigations aimed at refining therapeutic strategies and improving outcomes for patients with MSI-H CRC.

This study aimed to explore the potential of liquid biopsy as a diagnostic tool by integrating two key biomarkers, Circulating Tumor Cells (CTCs) and Circulating Tumor DNA (ctDNA), and to enhance the detection fidelity of prostate cancer. A dual biomarker analysis approach was employed to synergize the sensitivities of CTCs and ctDNA. Various genetic mutations of ctDNA and tissues were scrutinized, investigating their prevalence, co-existence, and mutual exclusivity. The findings uncovered a more intricate mutation landscape than previously anticipated, indicating a complex interplay between cellular and genetic aberrations in prostate cancer. Through harnessing the combined power of CTCs and ctDNA, our dual biomarker approach provides a more comprehensive understanding of prostate cancer genetics. This has the potential to revolutionize early detection and guide personalized therapeutic interventions.

目的 探讨晚期不可切除肝细胞癌患者应用仑伐替尼联合程序性死亡受体-1(PD-1)抑制剂治疗的疗效和安全性.方法 纳入2019 年2 月至2021 年 12 月在郑州大学第一附属医院应用仑伐替尼联合PD-1 抑制剂治疗的53 例和应用仑伐替尼治疗的50 例晚期不可切除肝细胞癌患者,比较观察2 组疗效和不良反应.结果 仑伐替尼联合治疗组客观缓解率为32.1%,疾病控制率为77.4%,仑伐替尼单药治疗组分别为 18.0%、72.0%,差异无统计学意义(χ2 =2.701,P =0.100;χ2 =0.391,P =0.532).仑伐替尼联合治疗组中位疾病无进展生存时间(9.4个月)长于仑伐替尼单药治疗组(7.5 个月),差异有统计学意义(χ2 =7.274,P =0.007).仑伐替尼联合治疗组中位总生存时间(19.2 个月)长于仑伐替尼单药治疗组(15.1 个月),差异有统计学意义(χ2 =6.202,P = 0.013).2 组最常见的不良反应均为乏力、高血压、食欲不振,最常见的Ⅲ级不良反应是高血压,尚未观察到Ⅳ级不良反应.结论 与仑伐替尼单药相比,仑伐替尼联合PD-1 抑制剂在晚期不可切除肝细胞癌患者中具有可靠的疗效和安全性.

We retrospectively analyzed the outcomes of 136 consecutive patients who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our center. Among them, 76 cases used hypomethylating agents (decitabine, n = 40; azacitidine, n = 36) as post-transplant maintenance therapy, whereas 60 contemporaneous patients did not adopt maintenance therapy. The 3-year incidences of relapse in two groups were 16.6% and 39.2% (p = .001). The 3-year OS and DFS in maintenance group were 84.0% and 78.6%, which were remarkably improved than in control group (60.0% and 58.0%) (p = .004, p = .011). Moreover, the 3-year relapse rates for patients receiving decitabine and azacitidine therapy were 8.5% and 25.0%, respectively (p = .019). Patients utilizing decitabine had more common possibility of grade 3-4 neutropenia than azacitidine (20.0% vs. 2.8%, p = .031). These results indicate that maintenance therapies using hypomethylating agents could reduce the risk of post-transplant recurrence, resulting into remarkable superior survival. Decitabine might lower relapse after allo-HSCT with somewhat more severe myelosuppression when being compared to azacitidine.

PurposeThe prognosis of liver cancer remains unfavorable nowadays, making the search for predictive biomarkers of liver cancer prognosis of paramount importance to guide clinical diagnosis and treatment. This study was conducted to explore more prognostic markers for most HCC.Patients and methodsA total of 330 patients were enrolled in this study according to the inclusion and exclusion criteria. Follow-up data were collected for all patients until the cutoff date of the study, February 2023. In addition, patient outcomes were assessed with progression-free survival (PFS) and overall survival (OS). All statistical analysis was conducted using R 4.2.0 software.ResultsUnivariate analysis illustrated that the GD [the product of gamma-glutamyl transpeptidase (GGT) concentration and D-dimer concentration, GD=GGT*D-dimer] levels were related to PFS (p<0.05) and OS (p<0.05). Kaplan–Meier survival curves and log-rank tests indicated a significant difference among different levels of GD (p<0.001). Multivariate analysis demonstrated GD as an independent prognostic factor for HCC. The C-indexes of nomogram were 0.77 and 0.76 in the training or validation cohort, respectively. Area Under the Curve (AUC) of 1-, 2-, 3-, and 4-year OS showed satisfactory accuracy, and the calibration curve illustrated brilliant consistence between the ideal and predicted values.ConclusionsHerein, it was demonstrated that GD was an independent prognostic factor for HCC and revealed the potential to predict the PFS and OS in patients with HCC. Moreover, the nomogram based on GD illustrated a satisfactory prediction ability in comparison to other models without GD.

The classic BCR-ABL1-negative myeloproliferative neoplasm (MPN) is a highly heterogeneous hematologic tumor that includes three subtypes, namely polycythemia vera (PV), essential thrombocytosis (ET), and primary myelofibrosis (PMF). Despite having the same JAK2V617F mutation, the clinical manifestations of these three subtypes of MPN differ significantly, which suggests that the bone marrow (BM) immune microenvironment may also play an important role. In recent years, several studies have shown that peripheral blood monocytes play an important role in promoting MPN. However, to date, the role of BM monocytes/macrophages in MPN and their transcriptomic alterations remain incompletely understood. The purpose of this study was to clarify the role of BM monocytes/macrophages in MPN patients with the JAK2V617F mutation. MPN patients with the JAK2V617F mutation were enrolled in this study. We investigated the roles of monocytes/macrophages in the BM of MPN patients, using flow cytometry, monocyte/macrophage enrichment sorting, cytospins and Giemsa-Wright staining, and RNA-seq. Pearson correlation coefficient analysis was also used to detect the correlation between BM monocytes/macrophages and the MPN phenotype. In the present study, the proportion of CD163+ monocytes/macrophages increased significantly in all three subtypes of MPN. Interestingly, the percentages of CD163+ monocytes/macrophages are positively correlated with HGB in PV patients and PLT in ET patients. In contrast, the percentages of CD163+ monocytes/macrophages are negatively correlated with HGB and PLT in PMF patients. It was also found that CD14+CD16+ monocytes/macrophages increased and correlated with MPN clinical phenotypes. RNA-seq analyses demonstrated that the transcriptional expressions of monocytes/macrophages in MPN patients are relatively distinct. Gene expression profiles of BM monocytes/macrophages suggest a specialized function in support of megakaryopoiesis in ET patients. In contrast, BM monocytes/macrophages yielded a heterogeneous status in the support or inhibition of erythropoiesis. Significantly, BM monocytes/macrophages shaped an inflammatory microenvironment, which, in turn, promotes myelofibrosis. Thus, we characterized the roles of increased monocytes/macrophages in the occurrence and progression of MPNs. Our findings of the comprehensive transcriptomic characterization of BM monocytes/macrophages provide important resources to serve as a basis for future studies and future targets for the treatment of MPN patients.

Exopolysaccharide (EPS), a bioproduct of lactic acid bacteria (LAB), has various health-promoting biological activities that may be beneficial for cancer therapy. This in vivo and in vitro study aimed to elucidate the anti-colorectal cancer (CRC) capacity of a homopolysaccharide EPS obtained from Weissella confusa J4-1 (EPSJ4-1) isolated from the faeces of healthy infants. We confirmed that EPSJ4-1 contained glucose and effectively suppressed the proliferation, migration, and invasion of CRC cells. EPSJ4-1 treatment significantly retarded the growth of HT-29 tumour xenografts without causing cytotoxicity to normal organs. EPSJ4-1 exerts an inhibitory effect on cell proliferation by inducing G0/G1 phase cell cycle arrest in CRC cells. Furthermore, EPSJ4-1 upregulated p21 levels and downregulated mutant p53 and cyclin kinase 2 levels. This is the first study to demonstrate the antitumour effects of EPS from W. confusa on CRC via cell cycle arrest and inhibition of cell migration and invasion, suggesting that EPSJ4-1 has the potential to be developed as a nutraceutical or pharmaceutical drug to prevent and treat CRC.

Microbiome is ubiquitous in human and distributed in not only normal organs such as gut, but also in tumor tissues of the host. Numerous studies have proven that the extratumoral microbiota (mainly gut microbiota) has a close relationship with the local and systemic immune systems of the host. The bacteria, viruses and fungi in gut can influence the activity of innate and adaptive immune cells, affecting the outcomes of immunotherapy. In addition to microbiota in the gut, special microbiota (intratumoral microbiota) exists in the tumor microenvironment (TME), which provides a critical niche for anaerobic or facultative anaerobic bacteria to colonize and proliferate. Intratumoral microorganisms or their metabolites can substantially improve the immunosuppressive of the TME, reactivate immune cells, or recruit activated immune cells, indicating a potential effect on immunotherapy. Furthermore, with the development of synthetic biology, some tumor-targeting bacteria can be used as a biological chassis for the accurate delivery of different immunotherapeutic agents to tumor core through genetic programming technologies, enriching immunotherapy paradigms. In this review, we summarize the recent developments in effect of human microbiota, especially microorganisms in the TME, on immunoregulation, and discuss their potential application in the field of cancer immunotherapy. We also describe the ways to take advantage of genetically engineered bacteria targeting the TME to strengthen the efficacy of immunotherapy against cancer. Additionally, the remaining questions and further directions for microbiota application in immunotherapy are also discussed.

The folate receptor-positive circulating tumor cell (FR+-CTC) count can be used to improve the diagnosis rate of lung cancer. The lymphocyte count (LC) and derived neutrophil-to-lymphocyte ratio (dNLR) are involved in inflammatory processes. Whether the FR+-CTC count combined with the dNLR or LC is helpful for diagnosing lung cancer recurrence is not clear. Sixty-eight patients who were initially diagnosed with lung cancer and received first-line treatment were included. The clinicopathological characteristics, routine blood examination results and CTC examination results of the patients were collected. The role of the complete blood count and FR+-CTC count in lung cancer treatment response and prognosis was analyzed. The FR+-CTC count after treatment was significantly correlated with the T stage (p=0.005). Multivariate analysis showed that the pathological type and FR+-CTC count were independent predictors of disease-or progression-free survival (DFS/PFS) in patients with lung cancer (p=0.010 and p=0.030, respectively). The FR+-CTC count, LC and dNLR predicted the recurrence of lung cancer (sensitivity and specificity of the FR+-CTC count, 69.2% and 71.4%; the LC, 50.0% and 88.5%; and the dNLR, 50.0% and 88.1%, respectively). The FR+-CTC count combined with the LC or dNLR improved the diagnostic rate of lung cancer recurrence (sensitivity and specificity of the FR+-CTC count plus the LC, 53.8% and 90.5%, and the FR+-CTC count plus the dNLR, 73.1% and 73.8%, respectively). When these three indicators were combined to predict lung cancer recurrence, the AUC value was 0.817. The FR+-CTC count combined with the dNLR and/or LC after treatment can improve the diagnostic rate of lung cancer recurrence. A higher FR+-CTC count predicts worse DFS/PFS in patients with lung cancer.