Radiation-based immunogenic vaccine combined with a macrophage "checkpoint inhibitor" for boosting innate and adaptive immunity against metastatic colon cancers.

Immunogenic dying tumor cells hold promising prospects as cancer vaccines to activate systemic immunity against both primary and metastatic tumors. Especially, X-ray- induced dying tumor cells are rich in highly immunogenic tumor-associated antigens and self-generated dsDNA as potent adjuvants. However, we found that the X-ray induction process can result in the excessive exposure of phosphatidylserine in cancer vaccines, which can specifically bind with the MerTK receptor on macrophages, acting as a "checkpoint" to facilitate immune silence in the tumor microenvironment. Therefore, we developed a novel strategy combining X-ray-induced cancer vaccines with UNC2250, a macrophage MerTK "checkpoint inhibitor," for treating peritoneal carcinomatosis in colon cancer. By incorporating UNC2250 into the treatment regimen, immunosuppressive efferocytosis of macrophages, which relies on MerTK-directed recognition of phosphatidylserine on vaccines, was effectively blocked. Consequently, the immune analysis revealed that this combination strategy promoted the maturation of dendritic cells and M1-like repolarization of macrophages, thereby simultaneously eliciting robust adaptive and innate immunity. This innovative approach utilizing X-ray-induced vaccines combined with a checkpoint inhibitor may provide valuable insights for developing effective cancer vaccines and immunotherapies targeting colon cancer.

Dying tumor cells-inspired vaccine for boosting humoral and cellular immunity against cancer.

Whole tumor cells can act as effective antigen depots and have been regarded as prospective candidate for cancer vaccines. However, the clinical outcomes of whole tumor cell vaccine were restricted by the poor immunogenicity and potential in vivo oncogenicity risks. Herein, a simple and effective cancer vaccine named frozen dying tumor cells (FDT) was constructed to initiate a cascade of immune attacks against cancer. By introducing immunogenic dying tumor cells and integrating cryogenic freezing technology, FDT was endowed with high immunogenicity, good in vivo safety, and long-time storage superiority. In syngeneic mice with malignant melanoma, FDT primed the polarization of follicular helper T cells and the differentiation of germinal center B cells in lymph nodes, and promoted the infiltration of cytotoxic CD8+ T cells in the tumor microenvironment, triggering the dual activation of humoral and cellular immunity. Of note, when combined with cytokines and immune checkpoint inhibitors, the FDT vaccine achieved 100% eradication of pre-existing tumors in mice, as demonstrated in the peritoneal metastasis model of colorectal carcinoma. Taken together, our work suggests an efficient cancer vaccine inspired by dying tumor cells and provides an alternative treatment candidate for cancer.

Chemodynamic/Photothermal Synergistic Cancer Immunotherapy Based on Yeast Microcapsule-Derived Au/Pt Nanoparticles.

In recent years, microbiota-based tumor immunotherapy has become a hotspot in cancer research. However, the use of microorganisms alone to activate the immune response for antitumor therapy was unsatisfactory. In this study, we biosynthesized gold nanoparticles (AuNPs) and platinum nanoparticles (PtNPs) based on yeast microcapsules to activate the immune response for antitumor treatment in synergy with chemodynamic therapy (CDT) and photothermal therapy (PTT). We generated AuNPs and PtNPs on yeast microcapsules (YAP) and fabricated nanoscale particles (Bre-YAP) by ultrasonic fragmentation and differential centrifugation. Bre-YAP retained the glucan component of yeast as an adjuvant; in the meantime, these two kinds of metal nanoparticles contained were excellent CDT and PTT mediators. By inspection, they could reach a high level of distribution in tumors and tumor-draining lymph nodes (TDLNs). Under the laser irradiation of tumors, this immunological nanomaterial significantly remodeled the microenvironments of tumors and TDLNs. The primary tumors were effectively inhibited or even eradicated, and the overall survival of mice was significantly improved as well. Therefore, yeast microcapsule-based Bre-YAP with immune properties could be used as an effective cancer treatment modality.

Influence of Adult Attachment on COVID-19 Vaccination Intention: The Mediating Roles of Help-Seeking Style and Professional Help-Seeking Behavior.

Vaccination against COVID-19 is regarded as one of the most promising interventions to control the pandemic. This study aimed to examine whether adult attachment affects an individual's COVID-19 vaccination intention and whether this relationship is mediated by help-seeking style and professional help-seeking behavior. A total of 401 Chinese adults participated in this online cross-sectional survey. The questionnaires for adult attachment (Depend, Close, and Anxiety), help-seeking style (dependency, autonomy, and avoidance), professional help-seeking behavior, and COVID-19 vaccination intention were rated on five-point or seven-point Likert scales, with satisfactory reliability (Cronbach's α values were all >0.80). Structural equation modelling was used to construct path models based on the above elements. Higher scores in the Depend (Effect = 0.047, SE = 0.018, 95% CI = [0.019, 0.093]) and Close dimensions of attachment (Effect = 0.028, SE = 0.014, 95% CI = [0.007, 0.065]) predicted a stronger dependency-oriented help-seeking style, which thus predicted greater vaccination intention. Higher scores in the Close dimension (Effect = 0.007, SE = 0.004, 95% CI = [0.001, 0.018]) and lower scores in the Anxiety dimension of attachment (Effect = -0.003, SE = 0.002, 95% CI = [-0.008, -0.001]) predicted a stronger autonomy-oriented help-seeking style and further predicted more professional help-seeking behaviors, which promoted greater COVID-19 vaccination intention. The results of this study indicate that help-seeking moderates the relationship between adult attachment and COVID-19 vaccination intention. Guiding help-seeking behavior for individuals with different attachment styles may be an entry point for improving COVID-19 vaccination intention.

Cell-Derived Biogenetic Gold Nanoparticles for Sensitizing Radiotherapy and Boosting Immune Response against Cancer.

The biosynthesis of nanomedicine has gained enormous attention and exhibited promising prospects, while the underlying mechanism and advantage remain not fully understood. Here, a cell-reactor based on tumor cells is developed to obtain biogenetic gold nanoparticles (Au@MC38) for sensitizing radiotherapy and boosting immune responses. It demonstrates that the intracellular biomineralization and exocytosis process of Au@MC38 can be regulated by the cellular metabolites level and other factors, such as glutathione and reactive oxygen species (ROS), autophagy, and UV irradiation. The elucidation of mechanisms may promote the understanding of interaction principles between nanoparticles and biosystems in the process of biosynthesis. Combined with radiotherapy, Au@MC38 strengthens the radiation-induced DNA damage and ROS generation, thus aggravating cell apoptosis and necrosis. Benefiting from homologous targeting and transcytosis effect, Au@MC38 demonstrates good tumor distribution. Local radiation-induced immunogenic cell death initiates an effective immune response. Especially, CD8a+ dendritic cells are significantly increased in mice that received combinatorial treatment. This radio-sensitization strategy has demonstrated the effective inhibition on primary and metastatic tumors, and achieved satisfactory survival benefit in combinatorial with immune checkpoint blockade. Thus, this bio-inspired synthetic strategy may impulse the development of biosynthesis and its therapeutic applications, contributing to a non-invasive and efficient modality for nanomedicine exploitation.