Evading host immunity killing is a critical step for virus survival. Inhibiting viral immune escape is crucial for the treatment of viral diseases. Serine/threonine kinase 39 (STK39) was reported to play an essential role in ion homeostasis. However, its potential role and mechanism in viral infection remain unknown. In this study, we found that viral infection promoted STK39 expression. Consequently, overexpressed STK39 inhibited the phosphorylation of interferon regulatory factor 3 (IRF3) and the production of type I interferon, which led to viral replication and immune escape. Genetic ablation or pharmacological inhibition of STK39 significantly protected mice from viral infection. Mechanistically, mass spectrometry and immunoprecipitation assays identified that STK39 interacted with PPP2R1A (a scaffold subunit of protein phosphatase 2A (PP2A)) in a kinase activity-dependent manner. This interaction inhibited DDB1 and CUL4 associated factor 1 (DCAF1)-mediated PPP2R1A degradation, maintained the stabilization and phosphatase activity of PP2A, which, in turn, suppressed the phosphorylation of IRF3, decreased the production of type I interferon, and then strengthened viral replication. Thus, our study provides a novel theoretical basis for viral immune escape, and STK39 may be a potential therapeutic target for viral infectious diseases.

Colorectal cancer is the most common malignant tumor of digestive tract, and BRAF V600E mutations occur in approximately 10% of patients with metastatic colorectal cancer (mCRC). Cancer patients harboring this mutation have a unique molecular profile and clinical phenotype; they show poor response to systemic chemotherapy, insensitivity to single BRAF inhibitor, and short survival rate. It is important to develop new therapeutic agents and clinical strategies to improve the prognosis of these patients. This review mainly introduces treatment methods for BRAF V600E-mutated mCRC and rationally derived combinations of targeted agents and immunotherapy.

Lung cancer is the leading cause of cancer death, and non-small cell lung cancer (NSCLC) accounts for 85%. Immunotherapy has significantly improved the clinical prognosis of patients with NSCLC. However, because of the complexity and heterogeneousness of the tumor microenvironment, only a subset of individuals can benefit from immunotherapy. Therefore, it is necessary to explore effective predictive biomarkers for immunotherapy of NSCLC. Tertiary lymphoid structure (TLS) is an ectopic lymphoid organ that is highly similar to secondary lymphoid organs (SLO), and the presence of TLS has been found to be closely associated with a good prognosis in immunotherapy for a variety of solid tumors, including NSCLC. This article provides a review of the prognostic role of tertiary lymphoid structures in immunotherapy of NSCLC, in order to offer references for screening suitable candidates for immunotherapy of NSCLC and develop personalized and precise treatment plans.
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Humans ; Carcinoma, Non-Small-Cell Lung/pathology* ; Tertiary Lymphoid Structures/pathology* ; Lung Neoplasms/pathology* ; Prognosis ; Immunotherapy ; Tumor Microenvironment

Background/Aims: Epstein-Barr virus-associated gastric cancers (EBVaGCs) have unique molecular and clinicopathological characteristics. The cyclic GMP-AMP synthase-stimulator of interferon genes (STING) pathway is recently recognized as the critical innate immunity against pathogens and tumors. STING is also a master regulator in the cancer-immunity cycle and targeting STING could synergize with existing immune-checkpoint therapies. However, the role of STING in GC, especially in EBVaGC, and its correlation with programmed death-ligand 1 (PD-L1) remain largely unclear. Methods: We collected 78 cases of EBVaGCs and 210 cases of EBV-negative GC (EBVnGC) from a total of 1,443 cases of GC analyzed by EBV-encoded small RNA in situ hybridization. We investigated STING and PD-L1 expression and their concomitant prognostic value in EBVaGCs and EBVnGCs using tissue microarray and immunohistochemistry. The effects of STING and PD-L1 expression on the overall survival of patients with EBVaGC or EBVnGC were assessed by univariate and multivariate analysis. Results: We found that both STING and PD-L1 exhibited significantly higher expression in the EBVaGCs than that in the EBVnGCs. The expression of STING was positively correlated with that of PD-L1 in EBVaGCs. Simultaneous negative expression of STING and PD-L1, and positive expression of STING were independent prognostic risk factors for EBVaGC and EBVnGC, respectively. Conclusions This is the first prognostic retrospective study of STING and PD-L1 expression and the prognosis among EBVaGC and EBVnGC. The expression and prognostic value of STING and PD-L1 are different in the two types of GCs. STING and PD-L1 are promising prognostic biomarkers and therapeutic targets for EBVaGC and EBVnGC.

Objective To investigate the relationship between genetic polymorphisms of ERCC1 and survival rate in advanced non-small cell lung cancer (NSCLC) patients treated with platinum based chemotherapy.Methods A total of 204 patients with advanced NSCLC were routinely treated by platinbased chemotherapy.The polymorphic genotypes were analyzed by MALDI-TOF-MS nethod using DNA samples isolated from peripheral blood before treatment.Besides,5 ％ samples werc extracted randomly for sequencing to test the accuracy of this method.To explored the association between SNP of ERCC1 (118) and prognosis to platinum-based chemotherapy in advanced NSCLC patients.Results Among 204 patients,61 achieved partial response,116 achieved stable response,and 27 achieved progressive disease.The overall response rate was 29.9 ％ (61/204).The effective rates of patients with the ERCC1 (118) C/C genotype,C/T + T/T genotype were 24.0 ％ (29/121) and 38.6 ％ (32/83),respectively,with significant difference (P ＜ 0.05).The response rate of ERCC1 (118) C/T allele carriers was 1.992-fold than that of C/C allele carriers (95 ％ confidence interval:1.083-3.650,P =0.025).MST,1-year survival and 2-year survival rates of patients with the ERCC1 (118) C/C genotype,C/T + T/T genotype were 9.0 months,34.7 ％ (42/121) and 4.1％ (5/121) vs 12.0 months,60.2 ％ (50/83) and 12.0 ％ (10/83),respectively,with significant difference (P ＜ 0.05).Conclusions Polymorphisms of ERCC1 might be associated with overall survival period in patients with advanced NSCLC after treatment with platin-based chemotherapy,which might be the predictive markers for overall survival.

Objective To assess the prognostic value of tumor burden measured by 18F-fluorodeoxy glucose-positron emission tomography ( FDG PET) imaging for stage Ⅲ NSCLC). Methods Fifty-six patients with lung cancer were analyzed, to whom staging PET-CT scans before treatment concurrent chemoradiotherapy and 2-year follow-up were performed. , Relationship between overall survival (OS) and metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) were determined.Results The estimated median OS for the cohort were 14. 5 months. Kaplan-Meier analysis showed that MTV had a significant effect on OS (x2 =5.42 ,P =0. 014). No significant relationship was found between SUVmax and OS ( x2 = 0. 74, P = 0. 391 ). According to multivariate Cox regression analysis, MTV and SUVmax wereassociatedwithincreaseddeath ( x2 = 5.54, P = 0.019; x2 = 4.47, P = 0.031 ). Conclusions This study shows that higher tumor burden assessed by PET MTV is an independent unfavorable prognostic factor in lung cancer, MTV is valuable for predicting overall survival and could be a prognostic factor.