Adjuvants for cancer mRNA vaccines in the era of nanotechnology: strategies, applications, and future directions.

Research into mRNA vaccines is advancing rapidly, with proven efficacy against coronavirus disease 2019 and promising therapeutic potential against a variety of solid tumors. Adjuvants, critical components of mRNA vaccines, significantly enhance vaccine effectiveness and are integral to numerous mRNA vaccine formulations. However, the development and selection of adjuvant platforms are still in their nascent stages, and the mechanisms of many adjuvants remain poorly understood. Additionally, the immunostimulatory capabilities of certain novel drug delivery systems (DDS) challenge the traditional definition of adjuvants, suggesting that a revision of this concept is necessary. This review offers a comprehensive exploration of the mechanisms and applications of adjuvants and self-adjuvant DDS. It thoroughly addresses existing issues mentioned above and details three main challenges of immune-related adverse event, unclear mechanisms, and unsatisfactory outcomes in old age group in the design and practical application of cancer mRNA vaccine adjuvants. Ultimately, this review proposes three optimization strategies which consists of exploring the mechanisms of adjuvant, optimizing DDS, and improving route of administration to improve effectiveness and application of adjuvants and self-adjuvant DDS.

Nanotheranostics in cancer lymph node metastasis: The long road ahead.

Lymph node metastasis (LNM) significantly impacts the prognosis of cancer patients. Despite significant advancements in diagnostic techniques and treatment modalities, clinical challenges continue to persist in the realm of LNM. These include difficulties in early diagnosis, limited treatment efficacy, and potential side effects and injuries associated with treatment. Nanotheranostics, a field within nanotechnology, seamlessly integrates diagnostic and therapeutic functionalities. Its primary goal is to provide precise and effective disease diagnosis and treatment simultaneously. The development of nanotheranostics for LNM offers a promising solution for the stratified management of patients with LNM and promotes the advancement of personalized medicine. This review introduces the mechanisms of LNM and challenges in its diagnosis and treatment. Furthermore, it demonstrates the advantages and development potential of nanotheranostics, focuses on the challenges nanotheranostics face in its application, and provides an outlook on future trends. We consider nanotheranostics a promising strategy to improve clinical effectiveness and efficiency as well as the prognosis of cancer patients with LNM.

Atezolizumab with chemotherapy in first-line treatment for metastatic urothelial cancer: a cost-effectiveness analysis.

Purpose: To evaluate the cost-effectiveness of atezolizumab plus chemotherapy as first-line treatment for metastatic urothelial cancer (mUC). Materials & methods: A Markov model was established for the analysis. Parametric survival models were used to fit to progression-free survival and overall survival data in the IMvigor130 study. A series of one-way and probabilistic sensitivity analyses were performed to test the robustness of the model. Results: The incremental cost-effectiveness ratios for atezolizumab plus chemotherapy versus chemotherapy alone were US$475,633.17 and $207,488.17 per quality-adjusted life year in the USA and China, respectively. Utility for the progression-free survival and progressive disease states, the cost of atezolizumab had the most significant impact on the incremental cost-effectiveness ratio. Conclusion: Atezolizumab plus chemotherapy is not a cost-effective treatment option as a first-line treatment for metastatic urothelial cancer.

High CD3D/CD4 ratio predicts better survival in muscle-invasive bladder cancer.

Background: Bladder cancer is a common malignancy that affects the human urinary tract. Muscle-invasive bladder cancer (MIBC) is aggressive and has poor prognosis. Previous studies have reported that the tumor-infiltrating lymphocytes (TILs) were associated with MIBC outcome; however, inconsistency remains and mRNA level TIL markers' prognostic significance in MIBC is unclear.  Materials and methods: In the present study, we reanalyzed data from four public datasets (the Cancer Genome Atlas for investigation; and CIT, GSE5287, and GSE31684 for validation) to examine the prognostic significance of CD3D, CD4, CD8A, CD3D/CD4 and CD3D/CD8A in MIBC.  Results: We found that the CD3D/CD4 ratio was a stable independent prognostic factor in MIBC (beta = -0.87, P = 0.025); high CD3D/CD4 ratio predicted better survival in MIBC, and the power of this association was much stronger in basal-squamous tumors (beta = -4.73, P = 2.67E-06). We also noted that the CD4 expression was significantly higher than CD3D (P < 0.05), indicating the presence of CD3-CD4+ cells which could be immune-suppressing. Conclusion: The CD3D/CD4 ratio can be viewed as a prognostic marker and a rough measurement for the interaction between immune-effecting CD3+ TILs and immune-suppressing CD3-CD4+ cells in MIBC, and this interaction may play a particularly important role in anti-cancer immunity in basal-squamous tumors as it has a very strong association with survival in this subtype, and may be used to select potential responders to immunotherapy.

The Role of COL5A2 in Patients With Muscle-Invasive Bladder Cancer: A Bioinformatics Analysis of Public Datasets Involving 787 Subjects and 29 Cell Lines.

Bladder cancer (BC) is one of the most common malignancies. Two previous studies identified collagen type V alpha 2 (COL5A2) as a potential biomarker in BC, both are simple reanalysis of a single transcriptomic dataset without subgroup analysis for muscle-invasive BC (MIBC). We focused in MIBC patients and explored the role of COL5A2 from an integration perspective, using refined methodology covering individual participant data meta-analysis and bioinformatics analysis. Eight transcriptomic datasets of 787 MIBC patients (including one dataset containing genomic mutation information) and two drug sensitivity datasets of 29 cell lines in which more than 250 compounds were analyzed. We found subjects with increased COL5A2 gene expression exhibited poorer prognosis, and the power analysis confirmed adequate sample size. FGFR3 was the only gene differential mutated between the COL5A2 high and low expression groups. Differential expression and co-expression network analysis suggested potential association between COL5A2 expression and essential pathways involved in cancer invasion and dissemination, including cell adhesion, extracellular matrix organization, and epithelial-mesenchymal transition. Coordinately, analysis of drug screening datasets and gene-drug interaction also revealed COL5A2 expression linked to cell morphogenesis, angiogenesis, blood vessel development, and urogenital development. The utility and feasibility of COL5A2 for clinically applicable prognosis prediction and risk classification and the exact underlying molecular mechanism should be further investigated in subsequent studies.