Efficacy of immune checkpoint inhibitors differs in various status of carcinoma: a study based on 29 cohorts with 3255 participants.

BACKGROUND: Pre-clinical data have revealed that viral infection, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV), and Human Papilloma virus (HPV), may lead to the development of "hot" or "immune-sensitive" tumors, which may impact the efficacy of immune checkpoint inhibitor (ICIs). Therefore, This study aimed to investigate the impact of viral status on the efficacy of ICIs. METHODS: Electronic databases were searched to identify relevant trials. The primary endpoints were overall survival (OS) and progression-free survival (PFS) measured by hazard ratio (HR). Stratified analyses were accomplished based on viral types, treatment regimens, and patient locations. RESULTS: A total of 3255 participants were recruited, including 252 cases of gastric cancer, 156 cases of nasopharyngeal carcinoma, 1603 cases of hepatocellular carcinoma, and 1244 cases of head and neck squamous cell carcinoma. Pooled results demonstrated a significant association between viral infection and favorable outcomes in patients receiving ICIs, including improved OS [HR = 0.67, 95%CI (0.57-0.79), P < 0.0001], increased ORR [OR = 1.43, 95%CI (1.14-1.80), P = 0.0018], and a trend toward enhanced PFS [HR = 0.75, 95%CI (0.56-1.00), P = 0.05]. In subgroup analyses, patients treated with ICIs who were exposed to HBV/HCV or HPV infection exhibited an evidently superior OS without heterogeneity, compared to those without infection. CONCLUSIONS: This study indicated that the presence of viral infection was evidently associated with improved outcomes in cancer patients undergoing ICIs, particularly in cases of HBV/HCV and HPV infections.

IL-1R8 expression in DLBCL regulates NK cell recruitment and influences patient prognosis.

The precise biological function of Interleukin-1 receptor 8 (IL-1R8) in diffuse large B-cell lymphoma (DLBCL) is still not well understood. Our goal is to decipher the profile of IL-1R8 expression status in DLBCL and to explore how IL-1R8 is involved in DLBCL progression. Utilizing a tissue microarray consisting of 70 samples of DLBCL tumors alongside 15 samples of tonsillitis, our investigation revealed a parallel expression profile of IL-1R8 between the tumor tissues and tonsillitis samples (p > 0.05). Nevertheless, an intriguing association emerged, as heightened expression of IL-1R8 correlated significantly with unfavorable survival outcomes in patients with DLBCL (p < 0.05). The status of IL-1R8 expression did not directly regulate proliferation (p > 0.05) and apoptosis (p > 0.05) in DLBCL cells via CCK8 and apoptotic assays. Subsequent chemotaxis analysis indicated that natural killer (NK) cell recruitment could be suppressed by IL-1R8 signaling in DLBCL, at least partially through CXCL1 inhibition (p < 0.05). The status of IL-1R8 expression in tumor tissues exhibited a negative correlation with the density of CD57+ NK cell infiltration (p < 0.05), while it did not demonstrate a significant association with CD3+ T cells (p > 0.05), CD68+ macrophages (p > 0.05), or S-100+ dendritic cells (p > 0.05). In line with this observation, elevated levels of NK cell infiltration demonstrated a significant positive correlation with improved overall survival (OS) among patients diagnosed with DLBCL (p < 0.05). Our data suggests the immuno-regulating potential of IL-1R8 through NK cell recruitment in DLBCL, providing novel insights into future immuno-modulating therapies.

Impact of probiotics use on clinical outcomes of immune checkpoint inhibitors therapy in cancer patients.

BACKGROUND: Dysbiosis of the gut microbiota can lead to impaired therapeutic effect of immune checkpoint inhibitors (ICIs). This study aimed to investigate the use of probiotics on the clinical outcomes of cancer patients receiving ICIs therapy. METHOD: PubMed, EMBASE, and the Cochrane Library database were searched to retrieve relevant studies that exploring the relationship between probiotics and the efficacy of ICIs. The primary endpoints included overall survival (OS) and progression-free survival (PFS), evaluated by the hazard rations (HRs) with 95% confidence intervals (CI), and the secondary endpoint was objective response rate (ORR), evaluated by the odd ratio (OR) with a 95% CI. RESULTS: A total of five studies including 1031 patients were eligible for analysis. Our results indicated that the use of probiotics was associated with a superior OS (HR = 0.50, 95% CI: 0.30-0.85, p = 0.01) and PFS (HR = 0.51, 95% CI: 0.42-0.61, p < 0.01), but had no relationship with ORR (OR = 2.11, 95%CI: 0.51-8.65, p = 0.30) in non-small cell lung cancer (NSCLC) patients. CONCLUSIONS: Probiotics were positively correlated with OS and PFS in NSCLC patients administrated with ICIs, but had no relationship with ORR.

Prognostic Value of Lymphocyte-to-Monocyte Ratio (LMR) in Cancer Patients Undergoing Immune Checkpoint Inhibitors.

Background: There is accumulating evidence that the lymphocyte-to-monocyte ratio (LMR) is related to the outcomes of cancer patients treated with immune checkpoint inhibitors (ICIs). However, the results remain controversial. Method: Electronic databases were searched to retrieve the studies that explore the relationship between LMR and the efficacy of ICIs. The primary endpoints were overall survival (OS) and progression-free survival (PFS), evaluated by the hazard ratios (HRs) with 95% confidence intervals (CI), and the secondary endpoints included disease control rate (DCR) and immune-related adverse events (irAEs), assessed by the odd ratios (ORs) with 95% CI. Results: A total of 27 studies involving 4,322 patients were eligible for analysis. The results indicated that increased LMR at baseline was associated with a superior OS (HR: 0.46, 95% CI: 0.39-0.56, p < 0.001), PFS (HR: 0.60, 95% CI: 0.49-0.74, p < 0.001), and DCR (OR: 3.16, 95% CI: 1.70-5.87, p < 0.001). Posttreatment LMR was linked to a better PFS (HR: 0.46, 95% CI: 0.29-0.71, p = 0.001), but failed to show this correlation in the analysis of OS and DCR. No correlation existed between LMR and irAEs regardless of the testing time (baseline or posttreatment). Subgroup analyses focusing on baseline LMR revealed that higher baseline LMR possessed a better OS in renal cell cancer (RCC) arm, nonsmall cell lung cancer (NSCLC) arm, multiple cancer arm, monotherapy arm, LMR <2 arm, LMR ≥2 arm, western countries arm, eastern countries arm, and anti-PD-1 arm. Higher baseline LMR correlated with better PFS in RCC arm, NSCLC arm, gastric cancer (GC) arm, multiple cancer arm, LMR <2 arm, LMR ≥2 arm, western countries arm, and eastern countries arm. Conclusions: Higher LMR at baseline was positively correlated with a superior OS, PFS, and DCR for ICIs, but not with irAEs.

Establishment of an immune microenvironment-based prognostic predictive model for gastric cancer.

AIMS: The prognoses of patients with gastric cancer(GC) vary in different stages, which is mainly due to the great differences in tumor and tumor microenvironment. This study is aimed to explore the specific differences. MAIN METHODS: Based on RNAseq-based expression data from The Cancer Genome Atlas database and GSE15459 and the latest biological process genelist, stage-related biological processes in gastric cancer were screened out. GSVA, LASSO-COX, univariate and multivariate Cox regression analysis, Kaplan-Meier survival analysis, and pearson correlation analysis were performed for prediction model construction, verification and functional annotation. KEY FINDINGS: The immune system process was enriched at advanced stages of gastric cancer. The tumor immune microenvironment-based prognostic risk score could be used to predict the overall survival and disease-free survival of patients with gastric cancer. The prognostic risk score was significantly associated with gastric cancer subtypes, inflammatory factors, and immune processes and a higher risk score indicated stronger tumor immunosuppression. SIGNIFICANCE: We found immune system processes were significantly elevated in advanced gastric cancer and established an immune-based prognostic predictive risk model for gastric cancer, which could reflect the degree of tumor immunosuppression and might be beneficial for clinical decision-making.

MiR-1271 Inhibits Cell Proliferation, Invasion and EMT in Gastric Cancer by Targeting FOXQ1.

BACKGROUND/AIMS: FOXQ1 overexpression has been reported to enhance tumor growth and invasion. However, the biological function of FOXQ1 and the mechanism underlying its upregulation in gastric cancer (GC) remain unknown. METHODS: QPCR was used to detect the expression of miR-1271 and FOXQ1 in specimens from GC patients. FOXQ1-siRNA, and miR- 1271 mimics and inhibitor were transfected into human MGC-803 and SGC-7901 cells. The transwell assay was used to examine the cell invasive ability. The regulation mechanism was confirmed by luciferase reporter assay. Markers of epithelial-mesenchymal transition (EMT) were detected by western blot analysis. RESULTS: MiR-1271 was downregulated in both GC tissues and GC cell lines. The expression of miR-1271 was inversely correlated with tumor size (P = 0.017), tumor stage (P = 0.035), lymph node metastasis (P = 0.018), and TNM stage (P = 0.025). Ectopic expression of miR-1271 dramatically suppressed GC cell proliferation, invasion, and EMT. Furthermore, FOXQ1 was identified as a direct target of miR-1271. Knockdown of FOXQ1 inhibited GC cell malignant behavior, whereas FOXQ1 overexpression partially restored the suppression effects of miR-1271. Additionally, miR-1271 expression was negatively correlated with FOXQ1 in GC tissues. CONCLUSIONS: MiR-1271 inhibits cell proliferation, invasion, and EMT in GC by directly suppressing FOXQ1 expression.

miR-320 enhances the sensitivity of human colon cancer cells to chemoradiotherapy in vitro by targeting FOXM1.

miR-320 expression level is found to be down-regulated in human colon cancer. To date, however, its underlying mechanisms in the chemo-resistance remain largely unknown. In this study, we demonstrated that ectopic expression of miR-320 led to inhibit HCT-116 cell proliferation, invasion and hypersensitivity to 5-Fu and Oxaliplatin. Also, knockdown of miR-320 reversed these effects in HT-29 cells. Furthermore, we identified an oncogene, FOXM1, as a direct target of miR-320. In addition, miR-320 could inactive the activity of Wnt/ß-catenin pathway. Finally, we found that miR-320 and FOXM1 protein had a negative correlation in colon cancer tissues and adjacent normal tissues. These findings implied that miR-320-FOXM1 axis may overcome chemo-resistance of colon cancer cells and provide a new therapeutic target for the treatment of colon cancer.