Metabolic mediators: microbial-derived metabolites as key regulators of anti-tumor immunity, immunotherapy, and chemotherapy.

The human microbiome has recently emerged as a focal point in cancer research, specifically in anti-tumor immunity, immunotherapy, and chemotherapy. This review explores microbial-derived metabolites, emphasizing their crucial roles in shaping fundamental aspects of cancer treatment. Metabolites such as short-chain fatty acids (SCFAs), Trimethylamine N-Oxide (TMAO), and Tryptophan Metabolites take the spotlight, underscoring their diverse origins and functions and their profound impact on the host immune system. The focus is on SCFAs' remarkable ability to modulate immune responses, reduce inflammation, and enhance anti-tumor immunity within the intricate tumor microenvironment (TME). The review critically evaluates TMAO, intricately tied to dietary choices and gut microbiota composition, assessing its implications for cancer susceptibility, progression, and immunosuppression. Additionally, the involvement of tryptophan and other amino acid metabolites in shaping immune responses is discussed, highlighting their influence on immune checkpoints, immunosuppression, and immunotherapy effectiveness. The examination extends to their dynamic interaction with chemotherapy, emphasizing the potential of microbial-derived metabolites to alter treatment protocols and optimize outcomes for cancer patients. A comprehensive understanding of their role in cancer therapy is attained by exploring their impacts on drug metabolism, therapeutic responses, and resistance development. In conclusion, this review underscores the pivotal contributions of microbial-derived metabolites in regulating anti-tumor immunity, immunotherapy responses, and chemotherapy outcomes. By illuminating the intricate interactions between these metabolites and cancer therapy, the article enhances our understanding of cancer biology, paving the way for the development of more effective treatment options in the ongoing battle against cancer.

Recombinant humanized type III collagen inhibits ovarian cancer and induces protective anti-tumor immunity by regulating autophagy through GSTP1.

Ovarian cancer (OC) is one of the leading causes of death from malignancy in women and lacks safe and efficient treatment. The novel biomaterial, recombinant humanized collagen type III (rhCOLIII), has been reported to have various biological functions, but its role in OC is unclear. This study aimed to reveal the function and mechanism of action of rhCOLIII in OC. We developed an injectable recombinant human collagen (rhCOL)-derived material with a molecular weight of 45 kDa, with a stable triple helix structure, high biocompatibility, water solubility and biosafety. The anti-tumor activity of rhCOLIII was comprehensively evaluated through in vitro and in vivo experiments. In vitro, our results showed that rhCOLIII inhibited the proliferation, migration, and invasion of ovarian cancer cells (OCCs), and induced apoptosis. In addition, rhCOLIII not only inhibited autophagy of OCCs but also increased the expression of MHC-1 molecule within OCCs. To further elucidate the mechanism of rhCOLIII in OC, we conducted joint analysis of RNA-Seq and proteomics, and found that rhCOLIII exerted anti-tumor function and autophagy inhibition by downregulating Glutathione S-transferase P1 (GSTP1). Furthermore, various rescue experiments were designed to demonstrate that rhCOLIII suppressed autophagy and proliferation of OCCs by mediating GSTP1. In vivo, we found that rhCOLIII could inhibit tumor growth and promote CD8+ T cell infiltration. Our results indicate that rhCOLIII has great anti-tumor potential activity in OC, and induces protective anti-tumor immunity by regulating autophagy through GSTP1. These findings illustrate the potential therapeutic prospects of rhCOLIII for OC treatment.

Effects of generational low dose-rate 137Cs internal exposure in descendant mice.

To quantitatively investigate the effects of chronic low-dose internal exposure to Cesium-137 on DNA damage, carcinogenicity, and offspring over multiple generations. The potential genetic risk in humans was predicted based on next-generation murine mutation rates to confirm the reasonableness of the current Cesium-137 dose limits for food. Cesium-137 (100 Bq/mL) was provided in drinking water to A/J mice, facilitating chronic, low-dose, low-dose-rate internal exposure through sibling mating over 25 generations (G25). The A/J mice were compared with a control strain with the same origin ancestry (no Cesium-137 water) for DNA double-strand breaks (DSBs), oxidative stress, chromosome aberrations, micronucleus test results, whole genome analysis, carcinogenicity, tumor growth rate, and immune competence. Compared to the control group, DNA DSBs and oxidative stress were significantly increased in the Cesium-137 group. However, no significant differences were observed between the groups regarding chromosome aberration, micronuclei, or the whole genome sequence mutation analysis. Although the carcinogenic rate did not differ between the groups, the rate of tumor growth was significantly suppressed in the Cesium-137 group. The anti-tumor cytokine trend in the Cesium-137 group likely contributed to this effect. No pathological or genetic effects were observed in the offspring of mice drinking water containing 100 Bq/mL Cesium-137 after G25. The contribution of low dose-rate radiation to carcinogenicity was not additive but growth-inhibitory. Although the negative data are not conclusive, these findings are deemed highly reliable.

Nuclear translocation of nucleotide enzyme Phosphoglucomutase 2 governs DNA damage response and anti-tumor immunity.

Targeting nucleotide enzymes emerges as a promising avenue for impeding tumor proliferation and fortifying anti-tumor immunogenicity. The non-canonical role of nucleotide enzymes remains poorly understood. In this study, we have identified that Phosphoglucomutase 2 (PGM2) rapidly accumulates at the DNA damage site to govern the DNA damage response mediated by the phosphorylation at Serine 165 and by forming a complex with Rho-associated coiled-coil-containing protein kinase 2 (ROCK2). Silencing PGM2 in Glioblastoma Multiforme (GBM) cells heightens DNA damage in vitro and enhances the sensitivity of temozolomide (TMZ) treatment by activating anti-tumor immunity in vivo. Furthermore, we demonstrate that pharmacological inhibition of ROCK2 synergistically complements TMZ treatment and pembrolizumab (PD-L1) checkpoint immunotherapy, augmenting anti-tumor immunity. This study reveals the non-canonical role of the nucleotide enzyme PGM2 in the regulation of DNA damage response and anti-tumor immunity, with implications for the development of therapeutic approaches in cancer treatment.

Novel Arf1 Inhibitors Drive Cancer Stem Cell Aging and Potentiate Anti-Tumor Immunity.

The small G protein Arf1 has been identified as playing a selective role in supporting cancer stem cells (CSCs), making it an attractive target for cancer therapy. However, the current Arf1 inhibitors have limited translational potential due to their high toxicity and low specificity. In this study, two new potent small-molecule inhibitors of Arf1, identified as DU101 and DU102, for cancer therapy are introduced. Preclinical tumor models demonstrate that these inhibitors triggered a cascade of aging in CSCs and enhance anti-tumor immunity in mouse cancer and PDX models. Through single-cell sequencing, the remodeling of the tumor immune microenvironment induced by these new Arf1 inhibitors is analyzed and an increase in tumor-associated CD8+ CD4+ double-positive T (DPT) cells is identified. These DPT cells exhibit superior features of active CD8 single-positive T cells and a higher percentage of TCF1+PD-1+, characteristic of stem-like T cells. The frequency of tumor-infiltrating stem-like DPT cells correlates with better disease-free survival (DFS) in cancer patients, indicating that these inhibitors may offer a novel cancer immunotherapy strategy by converting the cold tumor immune microenvironment into a hot one, thus expanding the potential for immunotherapy in cancer patients.

Iridium(III) Photosensitizers Induce Simultaneous Pyroptosis and Ferroptosis for Multi-Network Synergistic Tumor Immunotherapy.

The integration of pyroptosis and ferroptosis hybrid cell death induction to augment immune activation represents a promising avenue for anti-tumor treatment, but there is a lack of research. Herein, we developed two iridium(III)-triphenylamine photosensitizers, IrC and IrF, with the capacity to disrupt redox balance and induce photo-driven cascade damage to DNA and Kelch-like ECH-associated protein 1 (KEAP1). The activation of the absent in melanoma 2 (AIM2)-related cytoplasmic nucleic acid-sensing pathway, triggered by damaged DNA, leads to the induction of gasdermin D (GSDMD)-mediated pyroptosis. Simultaneously, iron homeostasis, regulated by the KEAP1/nuclear factor erythroid 2-related factor 2 (NRF2)/heme oxygenase 1 (HO-1) pathway, serves as a pivotal bridge, facilitating not only the induction of gasdermin E (GSDME)-mediated non-canonical pyroptosis, but also ferroptosis in synergy with glutathione peroxidase 4 (GPX4) depletion. The collaborative action of pyroptosis and ferroptosis generates a synergistic effect that elicits immunogenic cell death, stimulates a robust immune response and effectively inhibits tumor growth in vivo. Our work introduces the first metal-based small molecule dual-inducers of pyroptosis and ferroptosis for potent cancer immunotherapy, and highlights the significance of iron homeostasis as a vital hub connecting synergistic effects of pyroptosis and ferroptosis.

Reprogramming the immunosuppressive tumor microenvironment through nanomedicine: an immunometabolism perspective.

Increasing evidence indicates that immunotherapy is hindered by a hostile tumor microenvironment (TME) featured with deprivation of critical nutrients and pooling of immunosuppressive metabolites. Tumor cells and immunosuppressive cells outcompete immune effector cells for essential nutrients. Meanwhile, a wide range of tumor cell-derived toxic metabolites exerts negative impacts on anti-tumor immune response, diminishing the efficacy of immunotherapy. Nanomedicine with excellent targetability offers a novel approach to improving cancer immunotherapy via metabolically reprogramming the immunosuppressive TME. Herein, we review recent strategies of enhancing immunotherapeutic effects through rewiring tumor metabolism via nanomedicine. Attention is drawn on immunometabolic tactics for immune cells and stromal cells in the TME via nanomedicine. Additionally, we discuss future directions of developing metabolism-regulating nanomedicine for precise and efficacious cancer immunotherapy.

Clinical and molecular correlates of tumor aneuploidy in metastatic non-small cell lung cancer.

Recent studies have linked elevated tumor aneuploidy to anti-tumor immune suppression and adverse survival following immunotherapy. Herein, we provide supportive evidence for tumor aneuploidy as a biomarker of response to immunotherapy in patients with non-small cell lung cancer (NSCLC). We identify a dose-response relationship between aneuploidy score and patient outcomes. In two independent NSCLC cohorts (n = 659 patients), we demonstrate a novel association between elevated aneuploidy and non-smoking-associated oncogenic driver mutations. Lastly, we report enrichment of TERT amplification and immune-suppressive phenotypes of highly aneuploid NSCLC. Taken together, our findings emphasize a potentially critical role for tumor aneuploidy in guiding immunotherapy treatment strategies.

LAG-3 and PD-1 synergize on CD8+ T cells to drive T cell exhaustion and hinder autocrine IFN-γ-dependent anti-tumor immunity.

Overcoming immune-mediated resistance to PD-1 blockade remains a major clinical challenge. Enhanced efficacy has been demonstrated in melanoma patients with combined nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) treatment, the first in its class to be FDA approved. However, how these two inhibitory receptors synergize to hinder anti-tumor immunity remains unknown. Here, we show that CD8+ T cells deficient in both PD-1 and LAG-3, in contrast to CD8+ T cells lacking either receptor, mediate enhanced tumor clearance and long-term survival in mouse models of melanoma. PD-1- and LAG-3-deficient CD8+ T cells were transcriptionally distinct, with broad TCR clonality and enrichment of effector-like and interferon-responsive genes, resulting in enhanced IFN-γ release indicative of functionality. LAG-3 and PD-1 combined to drive T cell exhaustion, playing a dominant role in modulating TOX expression. Mechanistically, autocrine, cell-intrinsic IFN-γ signaling was required for PD-1- and LAG-3-deficient CD8+ T cells to enhance anti-tumor immunity, providing insight into how combinatorial targeting of LAG-3 and PD-1 enhances efficacy.

The cytokine Meteorin-like inhibits anti-tumor CD8+ T cell responses by disrupting mitochondrial function.

Tumor-infiltrating lymphocyte (TIL) hypofunction contributes to the progression of advanced cancers and is a frequent target of immunotherapy. Emerging evidence indicates that metabolic insufficiency drives T cell hypofunction during tonic stimulation, but the signals that initiate metabolic reprogramming in this context are largely unknown. Here, we found that Meteorin-like (METRNL), a metabolically active cytokine secreted by immune cells in the tumor microenvironment (TME), induced bioenergetic failure of CD8+ T cells. METRNL was secreted by CD8+ T cells during repeated stimulation and acted via both autocrine and paracrine signaling. Mechanistically, METRNL increased E2F-peroxisome proliferator-activated receptor delta (PPARδ) activity, causing mitochondrial depolarization and decreased oxidative phosphorylation, which triggered a compensatory bioenergetic shift to glycolysis. Metrnl ablation or downregulation improved the metabolic fitness of CD8+ T cells and enhanced tumor control in several tumor models, demonstrating the translational potential of targeting the METRNL-E2F-PPARδ pathway to support bioenergetic fitness of CD8+ TILs.

Loss of histone deubiquitinase Bap1 triggers anti-tumor immunity.

PURPOSE: Immunotherapy using PD-L1 blockade is effective in only a small group of cancer patients, and resistance is common. This emphasizes the importance of understanding the mechanisms of cancer immune evasion and resistance. METHODS: A genome-scale CRISPR-Cas9 screen identified Bap1 as a regulator of PD-L1 expression. To measure tumor size and survival, tumor cells were subcutaneously injected into both syngeneic WT mice and immunocompromised mice. The phenotypic and transcriptional characteristics of Bap1-deleted tumors were examined using flow cytometry, RNA-seq, and CUT&Tag-seq analysis. RESULTS: We found that loss of histone deubiquitinase Bap1 in cancer cells activates a cDC1-CD8+ T cell-dependent anti-tumor immunity. The absence of Bap1 leads to an increase in genes associated with anti-tumor immune response and a decrease in genes related to immune evasion. As a result, the tumor microenvironment becomes inflamed, with more cDC1 cells and effector CD8+ T cells, but fewer neutrophils and regulatory T cells. We also found that the elimination of Bap1-deleted tumors depends on the tumor MHCI molecule and Fas-mediated CD8+ T cell cytotoxicity. Our analysis of TCGA data further supports these findings, showing a reverse correlation between BAP1 expression and mRNA signatures of activated DCs and T-cell cytotoxicity in various human cancers. CONCLUSION: The histone deubiquitinase Bap1 could be used as a biomarker for tumor stratification and as a potential therapeutic target for cancer immunotherapies.

Boron Neutron Capture Therapy-Derived Extracellular Vesicles via DNA Accumulation Boost Antitumor Dendritic Cell Vaccine Efficacy.

Radiated tumor cell-derived extracellular vesicles (RT-EVs) encapsulate abundant DNA fragments from irradiated tumor cells, in addition to acting as integrators of multiple tumor antigens. Accumulating evidence indicates these DNA fragments from damaged cells are involved in downstream immune responses, but most of them are degraded in cells before incorporation into derived RT-EVs, thus the low abundance of DNA fragments limits immune responses of RT-EVs. Here, this study found that different radiations affected fates of DNA fragments in RT-EVs. Boron neutron capture therapy (BNCT) induced DNA accumulation in RT-EVs (BEVs) by causing more DNA breaks and DNA oxidation resisting nuclease degradation. This is attributed to the high-linear energy transfer (LET) properties of alpha particles from the neutron capture reaction of 10B. When being internalized by dendritic cells (DCs), BEVs activated the DNA sensing pathway, resulting in functional enhancements including antigen presentation, migration capacity, and cytokine secretion. After vaccination of the BEVs-educated DCs (BEV@BMDCs), the effector T cells significantly expanded and infiltrated into tumors, suggesting robust anti-tumor immune activation. BEV@BMDCs not only effectively inhibited the primary tumor growth and metastasis formation but also elicited long-term immune memory. In conclusion, a successful DC vaccine is provided as a promising candidate for tumor vaccine.

Targeting the glucocorticoid receptor-CCR8 axis mediated bone marrow T cell sequestration enhances infiltration of anti-tumor T cells in intracranial cancers.

Brain tumors such as glioblastomas are resistant to immune checkpoint blockade therapy, largely due to limited T cell infiltration in the tumors. Here, we show that mice bearing intracranial tumors exhibit systemic immunosuppression and T cell sequestration in bone marrow, leading to reduced T cell infiltration in brain tumors. Elevated plasma corticosterone drives the T cell sequestration via glucocorticoid receptors in tumor-bearing mice. Immunosuppression mediated by glucocorticoid-induced T cell dynamics and the subsequent tumor growth promotion can be abrogated by adrenalectomy, the administration of glucocorticoid activation inhibitors or glucocorticoid receptor antagonists, and in mice with T cell-specific deletion of glucocorticoid receptor. CCR8 expression in T cells is increased in tumor-bearing mice in a glucocorticoid receptor-dependent manner. Additionally, chemokines CCL1 and CCL8, the ligands for CCR8, are highly expressed in bone marrow immune cells in tumor-bearing mice to recruit T cells. These findings suggested that brain tumor-induced glucocorticoid surge and CCR8 upregulation in T cells lead to T cell sequestration in bone marrow, impairing the anti-tumor immune response. Targeting the glucocorticoid receptor-CCR8 axis may offer a promising immunotherapeutic approach for the treatment of intracranial tumors.

Hainanenin-1, an oncolytic peptide, triggers immunogenic cell death via STING activation in triple-negative breast cancer.

BACKGROUND: In triple-negative breast cancer (TNBC) therapy, insufficient tumor infiltration by lymphocytes significantly hinders the efficacy of immune checkpoint inhibitors. We have previously demonstrated that Hainanenin-1 (HN-1), a host defense peptide (HDP) identified from Hainan frog skin, induces breast cancer apoptosis and boots anti-tumor immunity via unknown mechanism. METHODS: We used in vitro experiments to observe immunogenic cell death (ICD) indicators in HN-1-treated TNBC cell lines, a mouse tumor model to verify HN-1 promotion of mice anti-tumor immune response, and an in vitro drug sensitivity test of patient-derived breast cancer cells to verify the inhibitory effect of HN-1. RESULTS: HN-1 induced ICD in TNBC in a process during which damage-associated molecular patterns (DAMPs) were released that could further increase the anti-tumor immune response. The secretion level of interleukin 2 (IL-2), IL-12, and interferon γ in the co-culture supernatant was increased, and dendritic cells (DCs) were activated via a co-culture with HN-1-pretreated TNBC cells. As a result, HN-1 increased the infiltration of anti-tumor immune cells (DCs and T lymphocytes) in the mouse model bearing both 4T1 and EMT6 tumors. Meanwhile, regulatory T cells and myeloid-derived suppressor cells were suppressed. In addition, HN-1 induced DNA damage, and double-strand DNA release in the cytosol was significantly enhanced, indicating that HN-1 might stimulate ICD via activation of STING pathway. The knockdown of STING inhibited HN-1-induced ICD. Of note, HN-1 exhibited inhibitory effects on patient-derived breast cancer cells under three-dimensional culture conditions. CONCLUSIONS: Collectively, our study demonstrated that HN-1 could be utilized as a potential compound that might augment immunotherapy effects in patients with TNBC.

The correlation between TRIM28 expression and immune checkpoints in CRPC.

This study delves into the unexplored realm of castration-resistant prostate cancer (CRPC) by investigating the role of TRIM28 and its intricate molecular mechanisms using high-throughput single-cell transcriptome sequencing and advanced bioinformatics analysis. Our comprehensive examination unveiled dynamic TRIM28 expression changes, particularly in immune cells such as macrophages and CD8+ T cells within CRPC. Correlation analyses with TCGA data highlighted the connection between TRIM28 and immune checkpoint expression and emphasized its pivotal influence on the quantity and functionality of immune cells. Using TRIM28 knockout mouse models, we identified differentially expressed genes and enriched pathways, unraveling the potential regulatory involvement of TRIM28 in the cGAS-STING pathway. In vitro, experiments further illuminated that TRIM28 knockout in prostate cancer cells induced a notable anti-tumor immune effect by inhibiting M2 macrophage polarization and enhancing CD8+ T cell activity. This impactful discovery was validated in an in situ transplant tumor model, where TRIM28 knockout exhibited a deceleration in tumor growth, reduced proportions of M2 macrophages, and enhanced infiltration of CD8+ T cells. In summary, this study elucidates the hitherto unknown anti-tumor immune role of TRIM28 in CRPC and unravels its potential regulatory mechanism via the cGAS-STING signaling pathway. These findings provide novel insights into the immune landscape of CRPC, offering promising directions for developing innovative therapeutic strategies.

Loss of ARID1A 'loops' in STING.

In a recent article, Maxwell et al. report that loss of tumor cell-specific AT-rich interaction domain 1A (ARID1A), a component of the chromatin remodeling SWI/SNF complex, triggers antitumor immunity via R-loop-mediated upregulation of the type-I interferon (IFN) pathway. These recent findings uncover a molecular mechanism underlying improved responses to immune checkpoint therapy (ICT) seen in patients harboring an ARID1A loss-of-function mutation.

Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor.

The gut microbiome significantly influences immune responses and the efficacy of immune checkpoint inhibitors. We conducted a clinical trial (NCT04264975) combining an anti-programmed death-1 (PD-1) inhibitor with fecal microbiota transplantation (FMT) from anti-PD-1 responder in 13 patients with anti-PD-1-refractory advanced solid cancers. FMT induced sustained microbiota changes and clinical benefits in 6 of 13 patients, with 1 partial response and 5 stable diseases, achieving an objective response rate of 7.7% and a disease control rate of 46.2%. The clinical response correlates with increased cytotoxic T cells and immune cytokines in blood and tumors. We isolated Prevotella merdae Immunoactis from a responder to FMT, which stimulates T cell activity and suppresses tumor growth in mice by enhancing cytotoxic T cell infiltration. Additionally, we found Lactobacillus salivarius and Bacteroides plebeius may inhibit anti-tumor immunity. Our findings suggest that FMT with beneficial microbiota can overcome resistance to anti-PD-1 inhibitors in advanced solid cancers, especially gastrointestinal cancers.

Lrp10 suppresses IL7R limiting CD8 T cell homeostatic expansion and anti-tumor immunity.

Signals emanating from the T-cell receptor (TCR), co-stimulatory receptors, and cytokine receptors each influence CD8 T-cell fate. Understanding how these signals respond to homeostatic and microenvironmental cues can reveal new ways to therapeutically direct T-cell function. Through forward genetic screening in mice, we discover that loss-of-function mutations in LDL receptor-related protein 10 (Lrp10) cause naive and central memory CD8 T cells to accumulate in peripheral lymphoid organs. Lrp10 encodes a conserved cell surface protein of unknown immunological function. T-cell activation induces Lrp10 expression, which post-translationally suppresses IL7 receptor (IL7R) levels. Accordingly, Lrp10 deletion enhances T-cell homeostatic expansion through IL7R signaling. Lrp10-deficient mice are also intrinsically resistant to syngeneic tumors. This phenotype depends on dense tumor infiltration of CD8 T cells, which display increased memory cell characteristics, reduced terminal exhaustion, and augmented responses to immune checkpoint inhibition. Here, we present Lrp10 as a new negative regulator of CD8 T-cell homeostasis and a host factor that controls tumor resistance with implications for immunotherapy.

Mechanisms by which obesity regulates inflammation and anti-tumor immunity in cancer.

Obesity is associated with an increased risk for 13 different cancers. The increased risk for cancer in obesity is mediated by obesity-associated changes in the immune system. Obesity has distinct effects on different types of inflammation that are tied to tumorigenesis. For example, obesity promotes chronic inflammation in adipose tissue that is tumor-promoting in peripheral tissues. Conversely, obesity inhibits acute inflammation that rejects tumors. Obesity therefore promotes cancer by differentially regulating chronic versus acute inflammation. Given that obesity is chronic, the initial inflammation in adipose tissue will lead to systemic inflammation that could induce compensatory anti-inflammatory reactions in peripheral tissues to suppress chronic inflammation. The overall effect of obesity in peripheral tissues is therefore dependent on the duration and severity of obesity. Adipose tissue is a complex tissue that is composed of many cell types in addition to adipocytes. Further, adipose tissue cellularity is different at different anatomical sites throughout the body. Consequently, the sensitivity of adipose tissue to obesity is dependent on the anatomical location of the adipose depot. For example, obesity induces more inflammation in visceral than subcutaneous adipose tissue. Based on these studies, the mechanisms by which obesity promotes tumorigenesis are multifactorial and immune cell type-specific. The objective of our paper is to discuss the cellular mechanisms by which obesity promotes tumorigenesis by regulating distinct types of inflammation in adipose tissue and the tumor microenvironment.

An Overview of Nanoparticle-Based Delivery Platforms for mRNA Vaccines for Treating Cancer.

With its unique properties and potential applications, nanoparticle-based delivery platforms for messenger RNA (mRNA) vaccines have gained significant attention in recent years. Nanoparticles have the advantages of enhancing immunogenicity, targeting delivery, and improving stability, providing a new solution for drug and vaccine delivery. In some clinical studies, a variety of nanoparticle delivery platforms have been gradually applied to a wide range of vaccine applications. Current research priorities are exploring various types of nanoparticles as vaccine delivery systems to enhance vaccine stability and immunogenicity. Lipid nanoparticles (LNPs) have shown promising potential in preclinical and clinical studies on the efficient delivery of antigens to immune cells. Moreover, lipid nanoparticles and other nanoparticles for nucleic acids, especially for mRNA delivery systems, have shown vast potential for vaccine development. In this review, we present various vaccine platforms with an emphasis on nanoparticles as mRNA vaccine delivery vehicles. We describe several novel nanoparticle delivery platforms for mRNA vaccines, such as lipid-, polymer-, and protein-based nanoparticles. In addition, we provide an overview of the anti-tumor immunity of nanovaccines against different tumors in cancer immunotherapy. Finally, we outline future perspectives and remaining challenges for this promising technology of nanoparticle-based delivery platforms for vaccines.