MRNA vaccines have tremendous potential to fight against cancer and viral diseases due to superiorities in safety, efficacy and industrial production. In recent decades, we have witnessed the development of different kinds of mRNAs by sequence optimization to overcome the disadvantage of excessive mRNA immunogenicity, instability and inefficiency. Based on the immunological study, mRNA vaccines are coupled with immunologic adjuvant and various delivery strategies. Except for sequence optimization, the assistance of mRNA-delivering strategies is another method to stabilize mRNAs and improve their efficacy. The understanding of increasing the antigen reactiveness gains insight into mRNA-induced innate immunity and adaptive immunity without antibody-dependent enhancement activity. Therefore, to address the problem, scientists further exploited carrier-based mRNA vaccines (lipid-based delivery, polymer-based delivery, peptide-based delivery, virus-like replicon particle and cationic nanoemulsion), naked mRNA vaccines and dendritic cells-based mRNA vaccines. The article will discuss the molecular biology of mRNA vaccines and underlying anti-virus and anti-tumor mechanisms, with an introduction of their immunological phenomena, delivery strategies, their importance on Corona Virus Disease 2019 (COVID-19) and related clinical trials against cancer and viral diseases. Finally, we will discuss the challenge of mRNA vaccines against bacterial and parasitic diseases.

The activation of the cGAS-STING pathway has tremendous potential to improve anti-tumor immunity by generating type I interferons. In recent decades, we have witnessed that producing dsDNA upon various stimuli is an initiative factor, triggering the cGAS-SING pathway for a defensive host. The understanding of both intracellular cascade reaction and the changes of molecular components gains insight into type I IFNs and adaptive immunity. Based on the immunological study, the STING-cGAS pathway is coupled to cancer biotherapy. The most challenging problem is the limited therapeutic effect. Therefore, people view 5, 6-dimethylxanthenone-4-acetic acid, cyclic dinucleotides and various derivative as cGAS-STING pathway agonists. Even so, these agonists have flaws in decreasing biotherapeutic efficacy. Subsequently, we exploited agonist delivery systems (nanocarriers, microparticles and hydrogels). The article will discuss the activation of the cGAS-STING pathway and underlying mechanisms, with an introduction of cGAS-STING agonists, related clinical trials and agonist delivery systems.

Checkpoint blockade therapy has shown significant therapeutic benefits and resulted in durable responses in patients with various tumors. However, accumulating evidence has demonstrated that 4‐29% of all patients with cancers with various histologies may suffer from tumor flare following such therapy. This novel tumor response pattern, termed hyperprogression, is a potentially deleterious side effect of checkpoint blockade therapy that accelerates disease progression in a subset of patients. In this review, we describe possible immune checkpoint blockade biomarkers and the epidemiology, different definitions, and predictors of hyperprogression based on the research findings and further present the available evidence supporting pathophysiological hypotheses that might explain hyperprogression during checkpoint blockade therapy. We also compare hyperprogression and pseudoprogression. Finally, we discuss areas requiring further study.

Background: Radiotherapy (RT) is a key treatment modality in cancer therapy, utilizing high‐energy radiation to directly kill tumor cells. Recent research has increasingly highlighted RT's potential to indirectly enhance antitumor immunity. However, this immune activation alone often fails to generate sustained systemic antitumor responses. In this study, we aimed to investigate the antitumor effects of combining cholesterolized toll‐like receptor 7 (TLR7) agonist liposomes, specifically 1V209‐Cho‐Lip, with RT. Methods: Mouse tumor models were used to assess the impact of combining 1V209‐Cho‐Lip with RT on tumor progression and modification of the tumor microenvironment. In vitro, primary mouse bone marrow‐derived dendritic cells (BMDCs) were utilized to investigate changes in function and the activated pathways through RNA sequencing. Additionally, we explored the role of oxidized mitochondrial DNA (ox‐mtDNA) released from irradiated tumor cells as a damage‐associated molecular pattern in modulating immune responses. The involvement of interleukin‐1β (IL‐1β) and the inflammasome pathway in the antitumor efficacy of the combined treatment was evaluated using Il‐1β ^−/− and cysteinyl aspartate specific proteinase 1 knockout ( Casp1 ^−/− ) mouse models. Results: The combination of 1V209‐Cho‐Lip and RT significantly inhibited tumor growth and induced antitumor immunity in tumor models. This combination therapy enhanced maturation, antigen presentation and IL‐1β secretion of dendritic cells (DCs) in vitro. Ox‐mtDNA released from irradiated tumor cells synergized with 1V209‐Cho‐Lip to activate the inflammasome pathway in DCs. The antitumor effect of the combined therapy was significantly reduced in Il‐1β ^−/− and Casp1 ^−/− mice. Conclusions: This study suggests that the combination of 1V209‐Cho‐Lip with RT might be a promising antitumor strategy and further studies are warranted to explore the clinical relevance of this combination therapy.

Background: Tumor-associated macrophages (TAMs) play a critical role in lung cancer progression, immune evasion, and treatment resistance within the unique, tissue-specific pulmonary immune microenvironment. However, a comprehensive bibliometric synthesis combining multi-database validation, quantitative time-series forecasting, and clinical translation integration remains lacking in the literature. Methods: Following a PRISMA-compliant two-stage screening protocol, literature published between 2005 and 2025 was retrieved from the Web of Science Core Collection (WOSCC) and Scopus. Bibliometric mapping and keyword clustering were performed using VOSviewer (v1.6.20), CiteSpace (v7.0.0), and Bibliometrix (v4.1.2). Predictive modeling of future annual output was conducted using an Auto-Regressive Integrated Moving Average (ARIMA) time-series framework. Methodological quality and network integrity were evaluated using CiteSpace structural metrics (Modularity Q and Mean Silhouette S). Results: Annual output increased slowly from 2005 to 2015 and accelerated sharply after 2018, reaching 439 articles in 2025, and is projected to reach 455 articles (95% CI 428-482) in 2026. China led in publication volume (1,970 articles in WOSCC) while the United States had the highest citation impact. Keyword clustering revealed a thematic progression from early genetic susceptibility and chemotherapy-related studies, through TAM polarization and metabolic reprogramming, to recent emphasis on lung adenocarcinoma, immune infiltration, and immunotherapy combinations. Citation bursts highlighted PD-1 expression on TAMs and recent interest in macrophage polarization. Fragmentary clusters on sarcopenia and animal models suggest underdeveloped but clinically relevant niches. Major funding came from the National Natural Science Foundation of China and the US National Cancer Institute. Conclusions: Lung cancer TAM research has moved from descriptive phenotyping toward mechanisms of heterogeneity, metabolism, and chemokine-driven immune regulation. Immunotherapy combinations and spatial technologies are current frontiers, but translational bottlenecks persist: lack of standardized TAM subset nomenclature, limited clinical validation, and neglect of small cell lung cancer. Cross-institutional collaboration and rigorous clinical testing are needed to bridge the gap between mechanistic discovery and patient benefit.