Fecal microbiome transplantation (FMT) from healthy donors is one of the techniques for restoration of the dysbiotic gut, which is increasingly being used to treat various diseases. Notably, mounting evidence in recent years revealed that FMT has made a breakthrough in the oncology treatment area, especially by improving immunotherapy efficacy to achieve antitumor effects. However, the mechanism of FMT in enhancing antitumor effects of immune checkpoint blockers (ICBs) has not yet been fully elucidated. This review systematically summarizes the role of microbes and their metabolites in the regulation of tumor immunity. We highlight the mechanism of action of FMT in the treatment of refractory tumors as well as in improving the efficacy of immunotherapy. Furthermore, we summarize ongoing clinical trials combining FMT with immunotherapy and further focus on refined protocols for the practice of FMT in cancer treatment, which could guide future directions and priorities of FMT scientific development.

MiR-199a-3p was significantly downregulated in the majority of human hepatocellular carcinoma (HCC) tissues and HCC cell lines. Yes associated protein 1 (YAP1) was overexpressed in human HCC, which promoted HCC development and progression by upregulating Jagged1 and activating the Notch pathway. We searched potential targets of miR-199a-3p with DIANA, TargetScan and PicTar tools, and found that YAP1 is one of the potential targets. Based on these findings, we speculated that miR-199a-3p might suppress HCC growth by targeting YAP1, downregulating Jagged1 and suppressing the Notch pathway. We determined the expression of miR-199a-3p and YAP1 by quantitative Real-Time PCR (qRT-PCR) and western blot assays, respectively, and found downregulation of miR-199a-3p and upregulation of YAP1 in HCC cell lines. Cell proliferation and apoptosis assays showed that miR-199a-3p suppresses HCC cell proliferation and promotes apoptosis, and knockdown of YAP1 has similar role. Furthermore, we verified that miR-199a-3p can directly target YAP1. We further investigated and confirmed that miR-199a-3p and YAP1 regulate HCC cell proliferation and apoptosis through Jagged1-Notch signaling. miR-199a-3p targets YAP1, downregulates Jagged1 and suppresses the Notch signaling to inhibit HCC cell proliferation and promote apoptosis. These findings provide new insights into the mechanism by which miR-199a-3p suppresses HCC cell proliferation and induces apoptosis.

Background: The evidence of transcatheter arterial chemoembolization (TACE) plus tyrosine kinase inhibitor and immune checkpoint inhibitor in unresectable hepatocellular carcinoma (HCC) was limited. This study aimed to evaluate the role of TACE plus apatinib (TACE + A) and TACE combined with apatinib plus camrelizumab (TACE + AC) in patients with unresectable HCC. Methods: This study retrospectively reviewed patients with unresectable HCC who received TACE + A or TACE + AC in 20 centers of China from January 1, 2019 to June 31, 2021. Propensity score matching (PSM) at 1:1 was performed to reduce bias. Treatment-related adverse events (TRAEs), overall survival (OS), progression-free survival (PFS), objective response rate (ORR) and disease control rate (DCR) were collected. Results: A total of 960 eligible patients with HCC were included in the final analysis. After PSM, there were 449 patients in each group, and the baseline characteristics were balanced between two groups. At data cutoff, the median follow-up time was 16.3 (range: 11.9–21.4) months. After PSM, the TACE + AC group showed longer median OS (24.5 vs 18.0 months, p < 0.001) and PFS (10.8 vs 7.7 months, p < 0.001) than the TACE + A group; the ORR (49.9% vs 42.5%, p = 0.002) and DCR (88.4% vs 84.0%, p = 0.003) of the TACE + AC group were also higher than those in the TACE + A group. Fever, pain, hypertension and hand-foot syndrome were the more common TRAEs in two groups. Conclusions: Both TACE plus apatinib and TACE combined with apatinib plus camrelizumab were feasible in patients with unresectable HCC, with manageable safety profiles. Moreover, TACE combined with apatinib plus camrelizumab showed additional benefit.

The tumor microenvironment orchestrates the sustained growth, metastasis and recurrence of cancer. As an indispensable component of the tumor microenvironment, cancer‐associated fibroblasts (CAF) are considered as an essential synthetic machine producing various tumor components, leading to cancer sustained stemness, drug resistance and tumor recurrence. Here, we developed a sustainable primary culture of lung cancer cells fed with lung cancer‐associated fibroblasts, resulting in enrichment and acquisition of drug resistance in cancer cells. Moreover, IGF2/AKT/Sox2/ABCB1 signaling activation in cancer cells was observed in the presence of CAF, which induces upregulation of P‐glycoprotein expression and the drug resistance of non‐small cell lung cancer cells. Our results demonstrated that CAF cells constitute a mechanism for cancer drug resistance. Thus, traditional chemotherapy combined with insulin‐like growth factor 2 (IGF2) signaling inhibitor may present an innovative therapeutic strategy for non‐small cell lung cancer therapy.

Background and Aim. Upper gastrointestinal bleeding is a threat to patients with gastric varices (GVs). Previous studies have concluded that both transjugular intrahepatic portosystemic shunt (TIPS) and balloon-occluded retrograde transvenous obliteration (BRTO) are effective treatments for patients with GV. We aimed to compare the efficiency and outcomes of these two procedures in GV patients through meta-analysis.Methods. The PubMed, Cochrane Library, EMBASE, and Web of Science databases were searched using the keywords: GV, bleeding, TIPS, and BRTO to identify relevant randomized controlled trials and cohort studies. The overall survival (OS) rate, imminent haemostasis rate, rebleeding rate, technical success rate, procedure complication rate (hepatic encephalopathy and aggravated ascites), and Child-Pugh score were evaluated. Randomized clinical trials and cohort studies comparing TIPS and BRTO for GV due to portal hypertension were included in our meta-analysis. Two independent reviewers performed data extraction and assessed the study quality. A meta-analysis was performed to calculate risk ratios (RRs), mean differences (MDs), and 95% CIs using random effects models.Results. A total of nine studies fulfilled the inclusion criteria. There was a significant difference between TIPS and BRTO in the OS rate (RR, 0.81 (95% CI, 0.66 to 0.98);P=0.03) and rebleeding rate (RR, 2.61 (95% CI, 1.75 to 3.90);P<0.00001). TIPS had a higher incidence rate of hepatic encephalopathy (RR, 16.11 (95% CI, 7.13 to 36.37);P<0.00001). There was no significant difference between TIPS and BRTO in the immediate haemostasis rate (RR, 0.99 (95% CI, 0.89 to 1.10);P=0.84), technical success rate (RR, 1.06 (95% CI, 0.98 to 1.16);P=0.16), aggravated ascites rate (RR, 0.60 (95% CI, 0.33 to 1.09);P=0.10), or Child-Pugh change (MD, 0.22 (95% CI, −0.21 to 0.65);P=0.31).Conclusions. In this meta-analysis, BRTO brought more benefits to patients, with a higher OS rate and lower rebleeding rate. BRTO is a feasible method for GVB.

To accurately predict the prognosis and further improve the clinical outcomes of bladder cancer (BLCA), we leveraged large‐scale data to develop and validate a robust signature consisting of small gene sets. Ten machine‐learning algorithms were enrolled and subsequently transformed into 76 combinations, which were further performed on eight independent cohorts (n = 1218). We ultimately determined a consensus artificial intelligence‐derived gene signature (AIGS) with the best performance among 76 model types. In this model, patients with high AIGS showed a higher risk of mortality, recurrence, and disease progression. AIGS is not only independent of traditional clinical traits [(e.g., American Joint Committee on Cancer (AJCC) stage)] and molecular features (e.g., TP53 mutation) but also demonstrated superior performance to these variables. Comparisons with 58 published signatures also indicated that AIGS possessed the best performance. Additionally, the combination of AIGS and AJCC stage could achieve better performance. Patients with low AIGS scores were sensitive to immunotherapy, whereas patients with high AIGS scores might benefit from seven potential therapeutics: BRD‐K45681478, 1S,3R‐RSL‐3, RITA, U‐0126, temsirolimus, MRS‐1220, and LY2784544. Additionally, some mutations (TP53 and RB1), copy number variations (7p11.2), and a methylation‐driven target were characterized by AIGS‐related multi‐omics alterations. Overall, AIGS provides an attractive platform to optimize decision‐making and surveillance protocol for individual BLCA patients.