Immunogenic cell death-based cancer vaccines: promising prospect in cancer therapy.

Tumor immunotherapy is a promising approach for addressing the limitations of conventional tumor treatments, such as chemotherapy and radiotherapy, which often have side effects and fail to prevent recurrence and metastasis. However, the effectiveness and sustainability of immune activation in tumor immunotherapy remain challenging. Tumor immunogenic cell death, characterized by the release of immunogenic substances, damage associated molecular patterns (DAMPs), and tumor associated antigens, from dying tumor cells (DTCs), offers a potential solution. By enhancing the immunogenicity of DTCs through the inclusion of more immunogenic antigens and stimulating factors, immunogenic cell death (ICD) based cancer vaccines can be developed as a powerful tool for immunotherapy. Integrating ICD nanoinducers into conventional treatments like chemotherapy, photodynamic therapy, photothermal therapy, sonodynamic therapy, and radiotherapy presents a novel strategy to enhance treatment efficacy and potentially improve patient outcomes. Preclinical research has identified numerous potential ICD inducers. However, effectively translating these findings into clinically relevant applications remains a critical challenge. This review aims to contribute to this endeavor by providing valuable insights into the in vitro preparation of ICD-based cancer vaccines. We explored established tools for ICD induction, followed by an exploration of personalized ICD induction strategies and vaccine designs. By sharing this knowledge, we hope to stimulate further development and advancement in the field of ICD-based cancer vaccines.

Adoptive cell therapy for solid tumors beyond CAR-T: Current challenges and emerging therapeutic advances.

Adoptive cellular immunotherapy using immune cells expressing chimeric antigen receptors (CARs) is a highly specific anti-tumor immunotherapy that has shown promise in the treatment of hematological malignancies. However, there has been a slow progress toward the treatment of solid tumors owing to the complex tumor microenvironment that affects the localization and killing ability of the CAR cells. Solid tumors with a strong immunosuppressive microenvironment and complex vascular system are unaffected by CAR cell infiltration and attack. To improve their efficacy toward solid tumors, CAR cells have been modified and upgraded by "decorating" and "pruning". This review focuses on the structure and function of CARs, the immune cells that can be engineered by CARs and the transformation strategies to overcome solid tumors, with a view to broadening ideas for the better application of CAR cell therapy for the treatment of solid tumors.

Codelivery of ERCC2 small interfering RNA and cisplatin with macrophage-derived mimetic nanovesicles for enhanced bladder cancer treatment.

Cisplatin-based chemotherapy plays a vital role in the management of muscle-invasive bladder cancer (MIBC); however, off-tumor toxicity and resistance often lead to cancer recurrence and eventual treatment failure. The loss of function of the nucleotide excision repair gene excision repair cross-complementing rodent repair deficiency gene 2 ( ERCC2 ) in cancer cells correlates with sensitivity to cisplatin, while its overexpression causes cisplatin resistance. Small interfering RNA (siRNA) knockdown of ERCC2 combined with cisplatin treatment may improve therapeutic outcomes in patients with bladder cancer. Here, we aimed to develop macrophage-derived mimetic nanovesicles (MNVs) as a nanoplatform for the simultaneous delivery of cisplatin and ERCC2 siRNA for enhancing the efficacy of bladder cancer chemotherapy. The cellular uptake, gene down-regulation, tumor inhibition effects, and biosafety of the synthesized nanodrugs (MNV-Co) as a synergistic therapeutic strategy for MIBC were evaluated in vitro and in vivo . The results indicated high efficacy of MNV-Co against MIBC and low off-tumor toxicity. Furthermore, by down-regulating ERCC2 mRNA and protein levels, MNV-Co improved chemosensitivity, promoted cancer cell apoptosis, and effectively suppressed tumor growth. This study presents a potential approach for delivering cisplatin and ERCC2 siRNA concurrently to treat bladder cancer using a biomimetic nanosystem.

Lycorine transfersomes modified with cell-penetrating peptides for topical treatment of cutaneous squamous cell carcinoma.

BACKGROUND: Topical anticancer drugs offer a potential therapeutic modality with high compliance for treating cutaneous squamous cell carcinoma (cSCC). However, the existing topical treatments for cSCC are associated with limited penetrating ability to achieve the desired outcome. Therefore, there remains an urgent requirement to develop drugs with efficient anticancer activity suitable for treating cSCC and to overcome the skin physiological barrier to improve the efficiency of drug delivery to the tumor. RESULTS: We introduced lycorine (LR) into the topical treatment for cSCC and developed a cell-penetrating peptide (CPP)-modified cationic transfersome gel loaded with lycorine-oleic acid ionic complex (LR-OA) (LR@DTFs-CPP Gel) and investigated its topical therapeutic effects on cSCC. The anti-cSCC effects of LR and skin penetration of LR-OA transfersomes were confirmed. Simultaneously, cationic lipids and modification of R5H3 peptide of the transfersomes further enhanced the permeability of the skin and tumor as well as the effective delivery of LR to tumor cells. CONCLUSIONS: Topical treatment of cSCC-xenografted nude mice with LR@DTFs-CPP Gel showed effective anticancer properties with high safety. This novel formulation provides novel insights into the treatment and pathogenesis of cSCC.

Metabolism heterogeneity in melanoma fuels deactivation of immunotherapy: Predict before protect.

Malignant melanoma is widely acknowledged as the most lethal skin malignancy. The metabolic reprogramming in melanoma leads to alterations in glycolysis and oxidative phosphorylation (OXPHOS), forming a hypoxic, glucose-deficient and acidic tumor microenvironment which inhibits the function of immune cells, resulting in a low response rate to immunotherapy. Therefore, improving the tumor microenvironment by regulating the metabolism can be used to improve the efficacy of immunotherapy. However, the tumor microenvironment (TME) and the metabolism of malignant melanoma are highly heterogeneous. Therefore, understanding and predicting how melanoma regulates metabolism is important to improve the local immune microenvironment of the tumor, and metabolism regulators are expected to increase treatment efficacy in combination with immunotherapy. This article reviews the energy metabolism in melanoma and its regulation and prediction, the integration of immunotherapy and metabolism regulators, and provides a comprehensive overview of future research focal points in this field and their potential application in clinical treatment.

Impact of Initial Feeding and Molting on Tachypleus tridentatus Gut Microbiota.

Tri-spine horseshoe crabs (HSCs) Tachypleus tridentatus have been facing the threat of population depletion for decades, and the physiology and microbiology of their early life stages are lacking. To explore what directs the change of juvenile T. tridentatus gut microbiota and how gut microbiota change, by using 16S rRNA sequencing of gut samples we detected the intestinal microbiome of juvenile HSCs and compared the impact of initial molting and initial feeding, as well as the effect of environment. Results showed that the predominant phyla in the gut microbial community of juvenile HSCs are Proteobacteria and Bacteroidetes. The richness and diversity of intestinal microbes greatly decreased after initial molting. Microbial-mediated functions predicted by PICRUSt showed that "Signal Transduction", "Cellular Processes and Signaling", "Infective Diseases" and "Digestive System" pathways significantly increased in 2nd instars. As for the effect of environment, the connection between living environment and the intestinal microbiome started to manifest after initial molting. Unexpectedly, initial feeding treatment slightly affected the intestinal microbiome of T. tridentatus in the early life stage, whereas the effect of initial molting was significant. The present study provided the first insight into the gut microbiota of T. tridentatus, and the findings led a new sight to explain what guide the change of gut microbiota.