Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel targeting LAG-3 drugs have also been approved in clinical application. With the widespread use of the drug, we must deeply analyze the dilemma of the agents and seek a breakthrough in the treatment prospect. Over the past decades, these agents have demonstrated dramatic efficacy, especially in patients with melanoma and non-small cell lung cancer (NSCLC). Nonetheless, in the field of a broad concept of solid tumours, non-specific indications, inseparable immune response and side effects, unconfirmed progressive disease, and complex regulatory networks of immune resistance are four barriers that limit its widespread application. Fortunately, the successful clinical trials of novel ICB agents and combination therapies, the advent of the era of oncolytic virus gene editing, and the breakthrough of the technical barriers of mRNA vaccines and nano-delivery systems have made remarkable breakthroughs currently. In this review, we enumerate the mechanisms of each immune checkpoint targets, associations between ICB with tumour mutation burden, key immune regulatory or resistance signalling pathways, the specific clinical evidence of the efficacy of classical targets and new targets among different tumour types and put forward dialectical thoughts on drug safety. Finally, we discuss the importance of accurate triage of ICB based on recent advances in predictive biomarkers and diagnostic testing techniques.

In the past decade, research on recombinant oncolytic viral agents in the treatment of solid tumors has evolved from the initial stage of simple genetic engineering to the current stage of multiple pipelines of parallel clinical application and combination therapy. Compared with T-VEC, the classical therapeutic agent that only expresses GM-CSF, which was approved in 2015, most new oncolytic virus designs include diverse gene constructs to reduce toxic effects, enhance multiple antitumor immunity, avoid immune clearance, or enhance tumor targeting. The single route of administration that activates the inflammatory tumor immune microenvironment by intratumoral injection is no longer sufficient to meet the treatment needs of refractory solid tumors. In this review, we illustrated the construction patterns of typical recombinant oncolytic viral agents and their latest clinical trial progress. Secondly, we summarized the underlying mechanisms of the combined application of antiviral and antitumor immunity in the field of solid tumor immunotherapy. Finally, we explored the feasibility of the intravenous application of oncolytic viruses and their future development directions. We believe that the diversified treatment design of oncolytic viruses will bring more surprises to the immunotherapy of refractory tumors.

The tumor microenvironment is a dynamic and balanced internal environment that accompanies the whole process of tumor development, invasion, and metastasis. Immune checkpoint therapy, chimeric antigen receptor cell therapy, oncolytic virus therapy, and bispecific antibody therapy are the most anticipated immunotherapy methods. These therapies break the microenvironment conducive to tumor growth by regulating anti-tumor immunity. The underlying characteristics of the tumor immune microenvironment are the key scientific issues to break the bottleneck of solid tumor immunotherapy. With the rapid development and application of single-cell sequencing technology and spatial oncology technology, scientists have gradually recognized more complex details of cell-cell interaction in the tumor microenvironment. We review the latest research progress in tumor immune escape, tumor metabolic reprogramming, and neuroimmunity [PubMed database published between 2000 and 21 May 2025]. We analyze the effects of these biological processes on anti-tumor immunity, to seek breakthroughs for the design of combined immune therapy. We also summarize the latest research on major immunotherapies mentioned above. Through the integration of frontier and hot basic scientific issues and the design of clinical trials, we hope to identify the potential combination treatment plan for immunotherapy to overcome the tumor microenvironment of solid tumors.

Background: Serious ovarian cancer (OvCa) is the most common histological type of epithelial OvCa with poor prognosis. Despite received optimal cytoreduction and standard chemotherapy, a large proportion of patients are forced to recurrence or death within three years. To identify exact prognostic biomarkers associated with overall survival (OS) is urgent requirements of exploring rapid tumor progression mechanisms and developing novel strategies for immunotherapy.Methods: The gene expression profiles of GSE49997, GSE9891 and TCGA were screened through rigorous criteria using R software and Bioconductor package. Weighted gene co-expression network analysis (WGCNA) was constructed to figure out gene clusters associated with OS. Protein-protein interaction (PPI) networks were built through STRING website. Prognostic values of potential biomarkers were validated using forest map and Kaplan-Meier analysis.Results: According to screening criteria, 788 samples and 10402 genes were reserved as the modeling dataset. We detected five modules related to OS and intersected 108 genes through WGCNA after random sampling. PPI network analysis, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed potential mechanisms of above biomarkers. Conclusions: Four exact biomarkers (CANT1, P4HB, DUS1L and SIRT7) were confirmed as independent predictors of survival in OvCa patients with success of debulking surgery, which might provide promising biomarkers for prognostic judgement in ovarian cancer.