Antitumor Immune Response Research Articles

A Spatially Distributed Microneedle System for Bioorthogonal T Cell-Guided Cancer Therapy.

Chimeric antigen receptor (CAR)-T cell therapy represents a promising strategy for cancer treatment. However, the diversity of solid tumor antigens and the poor infiltration of CAR-T cells significantly hinder the efficacy of CAR-T therapies against tumors. Here, a spatially distributed microneedle system (SDMNS) is developed that leverages bioorthogonal reactions to activate and guide endogenous T cells to tumors for effective destruction. The SDMNS consists of two dissolving microneedles, each loaded with complementary bioorthogonal groups and applied separately to lymph nodes and tumor sites. One microneedle loaded with two dibenzocyclooctyne (DBCO)-modified antibodies activates T cells and labels them with bioorthogonal groups in lymph nodes. The other microneedle, containing N-azidoacetylmannosamine-tetraacylated (Ac4ManNAz) for glycometabolic labeling of tumor cells, and the T cell chemotactic factor IP10, is applied directly to the tumor site. The in vivo studies demonstrate that SDMNS effectively directs the migration and infiltration of endogenous activated T cells into the tumors. Through a bioorthogonal click reaction, DBCO-modified T cells conjugate with azide (N3)-modified tumor cells, eliciting robust antitumor immune responses and durable immune memory. The SDMNS offers a novel strategy to overcomes tumor heterogeneity by facilitating the directed migration of endogenous T cells.

Ternary Schottky Junction for Sonocatalytic Water Splitting in Gas-Immunotherapy-Mediated Cancer Treatment.

Hydrogen therapy has shown new potential in cancer treatment, particularly in high-pressure and hypoxic areas, where it demonstrates the ability to alter the tumor microenvironment and regulate tumor metabolism. Hydrogen disrupts the mitochondrial function of cancer cells, interferes with their energy metabolism, and ultimately leads to energy depletion and apoptosis. In this study, a sonocatalyst (BPM), is designed to generate hydrogen and oxygen in situ within tumors, further enhancing the therapeutic efficacy. The mesocrystalline structure of BPM, composed of bismuth fluoride, polyoxometalates, and molybdenum carbide, significantly improves charge separation and electron transfer efficiency under ultrasound irradiation, resulting in an efficient water-splitting reaction. By simultaneously generating hydrogen and oxygen within the tumor microenvironment and depleting glutathione, BPM effectively triggers oxidative stress and alleviates hypoxia, thereby disrupting mitochondrial function and inhibiting energy metabolism in cancer cells. Additionally, BPM enhances antitumor immune responses by promoting dendritic cell maturation, activating T lymphocytes, and polarizing macrophages toward the M1 phenotype, reversing the immunosuppressive state of the tumor microenvironment. The results indicate that BPM holds potential for gas-immunotherapy combination treatments, offering a multifunctional strategy to improve cancer therapy outcomes.

A polysaccharide from Dendrobium devonianum induces antitumour immune responses by promoting TLR4-mediated M1 macrophage polarisation

A polysaccharide from <i>Dendrobium devonianum</i> induces antitumour immune responses by promoting TLR4-mediated M1 macrophage polarisation

Kindlin-2-mediated hematopoiesis remodeling regulates triple-negative breast cancer immune evasion.

Triple-negative breast cancer (TNBC) presents significant clinical challenges due to its limited treatment options and aggressive behavior, often associated with poor prognosis. This study focuses on Kindlin-2, an adaptor protein, and its role in TNBC progression, particularly in hematopoiesis-mediated immune evasion. TNBC tumors expressing high levels of Kindlin-2 induce a notable reshaping of hematopoiesis, promoting expansion of myeloid cells in bone marrow (BM) and spleen. This shift correlated with increased levels of neutrophils and monocytes in tumor-bearing mice over time. Conversely, genetic knockout of Kindlin-2 mitigated this myeloid bias and fostered T cell infiltration within the tumor microenvironment, indicating Kindlin-2's pivotal role in immune modulation. Further investigations revealed that Kindlin-2 deficiency led to reduced expression of PD-L1, a critical immune checkpoint inhibitor, in TNBC tumors. This molecular change sensitized Kindlin-2-deficient tumors to host anti-tumor immune responses, resulting in enhanced tumor suppression in immune-competent mouse models. Single-cell RNA sequencing, bulk RNA-seq, and immunohistochemistry data supported these findings by highlighting enriched immune-related pathways and increased infiltration of immune cells in Kindlin-2-deficient tumors. Therapeutically, targeting PD-L1 in Kindlin-2-expressing TNBC tumors effectively inhibited tumor growth, akin to the effects observed with genetic Kindlin-2 knockout or PD-L1-KO. Our data underscore Kindlin-2 as a promising therapeutic target in combination with immune checkpoint blockade to bolster anti-tumor immunity and counteract resistance mechanisms typical of TNBC and other immune evasive solid tumors. Implications: Kindlin-2 regulates tumor immune evasion through the systemic modulation of hematopoiesis and PD-L1 expression, which warrants therapeutic targeting of Kindlin-2 in TNBC patients.

Platycodon grandiflorum-derived extracellular vesicles suppress triple-negative breast cancer growth by reversing the immunosuppressive tumor microenvironment and modulating the gut microbiota

Despite the approval of several artificial nanotherapeutics for the treatment of triple-negative breast cancer (TNBC), significant challenges, including unsatisfactory therapeutic outcomes, severe side effects, and the high cost of large-scale production, still restrict their long-term application. In contrast, plant-derived extracellular vesicles (PEVs) exhibit promising potential in cancer therapy due to their negligible systemic toxicity, high bioavailability and cost- effectiveness. In this study, we developed an alternative strategy to inhibit TNBC via Platycodon grandiflorum (PG)-derived extracellular vesicles (PGEVs). The PGEVs were isolated by ultracentrifugation and sucrose gradient centrifugation method and contained adequate functional components such as proteins, lipids, RNAs and active molecules. PGEVs exhibited remarkable stability, tolerating acidic digestion and undergoing minimal changes in simulated gastrointestinal fluid. They were efficiently taken up by tumor cells and induced increased production of reactive oxygen species (ROS), leading to tumor cell proliferation inhibition and apoptosis, particularly in the TNBC cell line 4T1. Additionally, PGEVs facilitated the polarization of tumor-associated macrophages (TAMs) toward M1 phenotype and increased the secretion of pro-inflammatory cytokines. Further in vivo investigations revealed that PGEVs efficiently accumulated in 4T1 tumors and exerted significant therapeutic effects through boosting systemic anti-tumor immune responses and modulating the gut microbiota whether administered orally or intravenously (i.v.). In conclusion, these findings highlight PGEVs as a promising natural, biocompatible and efficient nanotherapeutic candidate for treating TNBC.Graphical

A covalent peptide-based lysosome-targeting protein degradation platform for cancer immunotherapy

The lysosome-targeting chimera (LYTAC) strategy provided a very powerful tool for the degradation of membrane proteins. However, the synthesis of LYTACs, antibody-small molecule conjugates, is challenging. The ability of antibody-based LYTACs to penetrate solid tumor is limited as well, especially to cross the blood-brain barrier (BBB). Here, we propose a covalent chimeric peptide-based targeted degradation platform (Pep-TACs) by introducing a long flexible aryl sulfonyl fluoride group, which allows proximity-enabled cross-linking upon binding with the protein of interest. The Pep-TACs platform facilitates the degradation of target proteins through the mechanism of recycling transferrin receptor (TFRC)-mediated lysosomal targeted endocytosis. Biological experiments demonstrate that covalent Pep-TACs can significantly degrade the expression of PD-L1 on tumor cells, dendritic cells and macrophages, especially under acidic conditions, and markedly enhance the function of T cells and tumor phagocytosis by macrophages. Furthermore, both in anti-PD-1-responsive and -resistant tumor models, the Pep-TACs exert significant anti-tumor immune response. It is noteworthy that Pep-TACs can cross the BBB and prolong the survival of mice with in situ brain tumor. As a proof-of-concept, this study introduces a modular TFRC-based covalent peptide degradation platform for the degradation of membrane protein, and especially for the immunotherapy of brain tumors.

A Phase 2 Study of Sotigalimab, a CD40 Agonist Antibody, Plus Concurrent Chemoradiation as Neoadjuvant Therapy for Esophageal and Gastroesophageal Junction Cancers.

Neoadjuvant chemoradiation (NCRT) followed by surgical resection represents a standard approach for patients with locally advanced esophageal/GEJ cancers. Sotigalimab is a high affinity CD40 agonist antibody capable of inducing and expanding anti-tumor immune responses by activating dendritic cells, T and B lymphocytes, NK cells, and M1 macrophages. This study examined the safety and efficacy of combining sotigalimab with NCRT in patients with esophageal or GEJ cancers. Patients with resectable (T1-3, Nx) adenocarcinoma(AC) or squamous cell carcinoma(SCC) of the esophagus or GEJ were eligible. T1N0 and cervical tumors were excluded. Study treatment: weekly carboplatin/paclitaxel with concurrent radiation 5040 cGy plus 3-4 doses of sotigalimab prior to Ivor-Lewis esophagectomy. Primary efficacy endpoint was pathologic complete response (path CR) rate. 33 patients were enrolled (AC 76%, SCC 24%; clinical stage III 67%). Ninety percent of patients received all planned doses of sotigalimab. The most common adverse events attributed to sotigalimab were nausea, fever/chills, fatigue, and cytokine release syndrome (CRS); most of these were Grade 1-2. Grade >3 CRS was observed in 3 pts (9%). Twenty-five of the 29 efficacy-evaluable patients underwent an R0 resection (87.9%), with an overall path CR rate of 37.9% (11/29). Post-tumor samples demonstrated increased infiltration and activation of dendritic cells, monocytes, and cytotoxic T cells compared to baseline. Sotigalimab combined with NCRT for esophageal or GEJ cancers was generally well tolerated and achieved path CR rates that compare favorably to historical data and are promising for this treatment strategy. NCT03165994.

Unlocking the Power of Photothermal Agents: A Universal Platform for Smart Immune NIR-Agonists for Precise Cancer Therapy.

Selective ablation of tumor cells allows safe eradication, thereby minimizing off-target damage, while specifically inducing immunogenic cell death (ICD) rather than commonly non-immunogenic apoptosis of tumor cells enables activation of anti-tumor immune response against residual cancer cells, including metastatic lesions. Herein, we present a general strategy leveraging a novel photothermal agent (PTA) that concomitantly enables precise tumor killing and activation of anti-tumor immunity. The unique PTA scaffold exhibits unexpected inherent endoplasmic reticulum (ER)-targeting capability and potent near-infrared (NIR) photothermal activity, inducing NIR-controlled immunogenic pyroptosis in various tumor cell lines via targeting ER stress in an oxygen-independent manner. Moreover, both ER-targeting and NIR-activity of our scaffold can be modulated on demand by chemical caging/uncaging, allowing quick activation with diverse biological and bioorthogonal molecular triggers. The potency of this universal platform is demonstrated via its application to develop a membrane protein-activatable NIR-agonist that selectively activates ICD in tumor sites while priming anti-tumor immunity, minimizing off-target effects and enhancing efficacy against mouse breast tumors. This versatile approach could lead to customization of various personalized and effective immune NIR-agonists for specific photoimmunotherapy applicable to diverse solid tumors.

Microglial reprogramming enhances antitumor immunity and immunotherapy response in melanoma brain metastases.

Melanoma is one of the tumor types with the highest risk of brain metastasis. However, the biology of melanomabrain metastasis and the role of the brain immune microenvironment in treatment responses are not yet fully understood. Using preclinical models and single-cell transcriptomics, we have identified a mechanism that enhances antitumor immunity in melanoma brain metastasis. We show that activation of the Rela/Nuclear Factor κB (NF-κB) pathway in microglia promotes melanoma brain metastasis. Targeting this pathway elicits microglia reprogramming toward a proinflammatory phenotype, which enhances antitumor immunity and reduces brain metastatic burden. Furthermore, we found that proinflammatory microglial markers in melanoma brain metastasis are associated with improved responses to immune checkpoint inhibitors in patients and targeting Rela/NF-κB pathway in mice improves responses to these therapies in the brain, suggesting a strategy to enhance antitumor immunity and responses to immune checkpoint inhibitors in patients with melanoma brain metastasis.

From heterogeneity to prognosis: understanding the complexity of tertiary lymphoid structures in tumors.

Tertiary lymphoid structures (TLSs) are aberrant lymphoid tissues found in persistent inflammatory settings, including malignancies, autoimmune disorders, and transplanted organs. The organization and architecture of TLS closely resemble that of secondary lymphoid organs (SLOs). The formation of TLS is an ongoing process, with varying structural features observed at different stages of maturation. The tumor microenvironment (TME) is a multifaceted milieu comprising cells, molecules, and extracellular matrix components in close proximity to the neoplasm. TLS within the TME have the capacity to actively elicit anti-tumor immune responses. TLSs exhibit tumor-specific and individual-specific characteristics, leading to varying immune responses towards tumor immunity based on their distinct cellular components, maturity levels, and spatial distribution. Cell interaction is the foundational elements of tumor immunity. Despite differences in the cellular composition of TLS, B cells and T cells are the main components of tumor-associated TLS。Recent research has highlighted the significance of diverse subtypes of B cells and T cells within TLSs in influencing the therapeutic outcomes and prognostic indicators of individual tumors. This review elucidates the diversity of TLS in terms of cellular composition, developmental stage, anatomical location, and the influence of cytokines on their initiation and progression. Furthermore, the article examines the involvement of B and T cells within TLS and the significance of TLS in relation to tumor prognosis.

Leveraging the Immunological Impacts of Irreversible Electroporation as a New Frontier for Cancer Therapy.

Irreversible electroporation (IRE) is a nonthermally mediated tissue ablation modality that makes use of short pulsed electric fields to destroy cancerous lesions in situ. In the past two decades, IRE has established itself not only as an effective means to ablate small, unresectable tumor masses but also as a tool particularly qualified to modulate the tumor microenvironment in a way that dismantles pathways of cancer immunosuppression and permits the development of a systemic antitumor immune response. However, despite its immune-stimulating tendencies, for most cancers conventional IRE alone is insufficient to establish an immune response robust enough to fully eliminate disseminated disease and prevent recurrence. Here, we describe the current understanding of the histological and immunological effects of IRE, as well as recent efforts to optimize IRE parameters and develop rational combination therapies to increase the efficacy of the resulting immune response.

Phase I study of intratumoral administration of CV8102 in patients with advanced melanoma, squamous cell carcinoma of the skin, squamous cell carcinoma of the head and neck, or adenoid cystic carcinoma

BackgroundCV8102, a toll-like receptor 7/8 and RIG I agonist, has demonstrated antitumor immune responses in preclinical studies. We investigated intratumoral (IT) administration of CV8102 in patients with anti-programmed cell death...

Tumor-Intrinsic SIRPA Drives Pyroptosis Evasion in Head and Neck Cancer.

Pyroptosis, a gasdermin-mediated immunogenic cell death, has been shown to elicit adaptive antitumor immune responses, thereby augmenting the response to cancer immunotherapy when pyroptosis is therapeutically activated. However, despite increased gasdermin E (GSDME) expression, significant pyroptosis remains elusive in certain tumor types, and the underlying regulatory mechanisms are poorly understood. In this study, we observed high signal regulatory protein α1 (SIRPA) expression in head and neck squamous cell carcinoma (HNSCC) cells, a target in cancer immunotherapy. Intriguingly, SIRPA inhibition markedly augmented pyroptosis activity in tumor tissues and modulated tumor growth in a HNSCC mouse model. Subsequent investigations revealed that SIRPA knockout upregulated GSDME expression and potentiated cisplatin-induced pyroptosis in cancer cells. Integrative transcriptomics and metabolomics analysis suggested that the SIRPA knockout profoundly altered protein ubiquitination and augmented argininosuccinic acid levels in cancer cells. Specifically, we demonstrated that ubiquitin-specific peptidase 18 (USP18), a deubiquitinating enzyme, targets GSDME for deubiquitination and that USP18 knockdown suppressed cisplatin-induced pyroptosis. Notably, we found that succinylation of GSDME, which is mediated by succinyl-CoA, promotes GSDME cleavage without affecting caspase-3 activation. Further experiments indicated that SIRPA expression in tumor cells can decrease the antitumor efficacy of chemotherapy and immunotherapy in HNSCC mouse models. In summary, our findings reveal a novel mechanism of pyroptosis evasion in HNSCC, whereby tumor-intrinsic SIRPA enhances GSDME ubiquitylation and inhibits its succinylation. These insights suggest that inhibiting SIRPA expression may improve the efficacy of immunotherapy for HNSCC by inducing pyroptosis.

Mitochondria-targeting of oxidative phosphorylation inhibitors to alleviate hypoxia and enhance anticancer treatment efficacy.

Hypoxia is a common feature of solid tumors and is associated with a poor response to anticancer therapies. Hypoxia also induces metabolic changes, such as a switch to glycolysis. This glycolytic switch causes acidification of the tumor microenvironment (TME), thereby attenuating the anticancer immune response. A promising therapeutic strategy to reduce hypoxia and thereby sensitize tumors to irradiation and/or antitumor immune responses is pharmacological inhibition of oxidative phosphorylation (OXPHOS). Several OXPHOS inhibitors (OXPHOSi) have been tested in clinical trials. However, moderate responses and/or substantial toxicity has hampered clinical implementation. OXPHOSi tested in clinical trials inhibit the oxidative metabolism in tumor cells as well as healthy cells. Therefore, new strategies are needed to improve the efficacy of OXPHOSi while minimizing side effects. To enhance the therapeutic window, available OXPHOSi have, for instance, been conjugated to triphenylphosphonium (TPP+) to preferentially target the mitochondria of cancer cells, resulting in increased tumor uptake compared to healthy cells, as cancer cells have a higher mitochondrial membrane potential. However, OXPHOS inhibition also induces reactive oxygen species (ROS), and subsequent antioxidant responses, which may influence the efficacy of therapies, such as platinum-based chemotherapy and radiotherapy. Here, we review the limitations of the clinically tested OXPHOSi metformin, atovaquone, tamoxifen, BAY 87-2243 and IACS-010759 and the potential of mito-targeted OXPHOSi and their influence on ROS production. Furthermore, the effect of the mitochondria-targeting moiety TPP+ on mitochondria is discussed as this affects mitochondrial bioenergetics.

Integrative analysis of immunogenic PANoptosis and experimental validation of cinobufagin-induced activation to enhance glioma immunotherapy.

Glioma, particularly glioblastoma (GBM), is a highly aggressive tumor with limited responsiveness to immunotherapy. PANoptosis, a form of programmed cell death merging pyroptosis, apoptosis, and necroptosis, plays an important role in reshaping the tumor microenvironment (TME) and enhancing immunotherapy effectiveness. This study investigates PANoptosis dynamics in glioma and explores the therapeutic potential of its activation, particularly through natural compounds such as cinobufagin. We comprehensively analyzed PANoptosis-related genes (PANoRGs) in multiple glioma cohorts, identifying different PANoptosis patterns and constructing the PANoptosis enrichment score (PANoScore) to evaluate its relationship with patient prognosis and immune activity. Cinobufagin, identified as a PANoptosis activator, was evaluated for its ability to induce PANoptosis and enhance anti-tumor immune responses both in vitro and in vivo GBM models. Our findings indicate that high PANoScore gliomas showed increased immune cell infiltration, particularly effector T cells, and enhanced sensitivity to immunotherapies. Cinobufagin effectively induced PANoptosis, leading to increased immunogenic cell death, facilitated tumor-associated microglia/macrophages (TAMs) polarization towards an M1-like phenotype while augmenting CD4+/CD8 + T cell infiltration and activation. Importantly, cinobufagin combined with anti-PD-1 therapy exhibited significant synergistic effects and prolonged survival in GBM models. These findings highlight the therapeutic potential of PANoptosis-targeting agents, such as cinobufagin, in combination with immunotherapy, offering a promising approach to convert "cold" tumors into "hot" ones and improving glioma treatment outcomes.

A Novel Multicompartment Barrier-Free Microfluidic Device Reveals the Impact of Extracellular Matrix Stiffening and Temozolomide on Immune-Tumor Interactions in Glioblastoma.

The immune system plays a crucial role in shaping the glioblastoma tumor microenvironment, characterized by its complexity and dynamic interactions. Understanding the tumor-immune crosstalk is essential for advancing cancer research and therapeutic development. Here, a novel multicompartment, barrier-free microfluidic device is presented that overcomes the limitations of existing models by enabling direct tumor-immune interactions without physical barriers, preserving natural immune cell infiltration. This platform supports the independent and simultaneous culture of tumor and immune cells, replicating the healthy-tumoral stroma interface, and allows investigating the effect of matrix stiffness and chemotherapy on both populations. The findings reveal that increased collagen concentration promotes tumor invasiveness while impairing immune cell infiltration. Additionally, temozolomide treatment reduces immune cell motility but enhances anti-tumor immune responses. These insights highlight the critical roles of extracellular matrix mechanics and chemotherapy in tumor progression and immune modulation, establishing this device as a powerful tool for studying glioblastoma-immune dynamics and evaluating therapeutic strategies.

Oncolytic Viruses in Ovarian Cancer: Where Do We Stand? A Narrative Review

Ovarian cancer (OC) remains the most lethal gynecologic malignancy with limited effective treatment options. Oncolytic viruses (OVs) have emerged as a promising therapeutic approach for cancer treatment, capable of selectively infecting and lysing cancer cells while stimulating anti-tumor immune responses. Preclinical studies have demonstrated significant tumor regression and prolonged survival in OC models using various OVs, such as herpes simplex. Early-phase clinical trials have shown a favorable safety profile, though the impact on patient survival has been modest. Current research focuses on combining OVs with other treatments like immune checkpoint inhibitors to enhance their efficacy. We provide a comprehensive overview of the current understanding and future directions for utilizing OVs in the management of OC.

Integrin‐Targeted, Activatable Nanophototherapeutics for Immune Modulation: Enhancing Photoimmunotherapy Efficacy in Prostate Cancer Through Macrophage Reprogramming

ABSTRACTProstate cancer is an epithelial malignancy with a high incidence among elderly men. Photochemistry‐based dye photodrugs (known as photosensitizers) offer a promising clinical approach for treating tumors. These agents work by inducing immunogenic cell death (ICD), which activates antitumor immune response. This approach is favored owing to its minimal invasiveness, low toxicity, and high efficiency. However, the immunosuppressive microenvironment of characteristics of “cold” tumors significantly restricts the clinical efficacy of photodrugs. Developing an advanced nanocarrier system to deliver photodrugs and immune agonists for efficient drug delivery to tumor lesion sites and to reshape the immunosuppressive microenvironment is crucial in clinical practice. Therefore, in this study, we designed an integrin‐targeted, activatable nano photodrug co‐assembly with an immune agonist (RPST@IMQ) for enhancing photoimmunotherapy in prostate cancer via the reprogramming of tumor‐associated macrophages. The active‐targeted nanosystem enhanced the dosage of photodrug at the lesion site through systemic administration. High doses of glutathione at the tumor site cleaved the disulfide bonds of RPST@IMQ, releasing the photodrug and the immune agonist imiquimod (IMQ). Under photoirradiation, the photodrug generated significant doses of singlet oxygen to eliminate tumor cells, thereby inducing ICD to activate antitumor immune responses. Simultaneously, the released IMQ reprograms immunosuppressive M2‐type tumor‐associated macrophages (TAMs) in the tumor microenvironment into M1‐type TAMs with tumor‐killing capabilities, thereby converting “cold” tumors into “hot” tumors. This conversion enhances the therapeutic efficacy against primary and distant tumors in vivo. This study offers new insights into the development of innovative, smart, activatable nano photodrugs to enhance anticancer therapeutic outcomes.

Functionalized aluminum hydroxide-based self-adjuvanted nanovaccine orchestrates antitumor immune responses via Dectin-1 signaling.

Self-adjuvanted vaccine delivery platforms possess potential for targeted delivery of antigens and initiation of potent immune responses. Although aluminum-containing adjuvants have been approved and widely used in human vaccines, their effectiveness in inducing Th1-type immune responses is far from satisfactory. To facilitate antigen delivery and activate potent antitumor immune responses, a self-adjuvanted nanovaccine (CPBG-Al@OVA) is constructed by functionalizing aluminum hydroxide with β-1,3-glucan, which recognizes pattern recognition receptors via Dectin-1. Carboxymethyl-phosphorylated β-1,3-glucan (CPBG) has been synthesized and optimized to achieve superior adjuvanticity while maintaining water solubility. CPBG then self-assembles with aluminum hydroxide and the targeted antigen, leading to the formation of a nanovaccine CPBG-Al@OVA. Owing to the favorable nanoscale size distribution, CPBG-Al@OVA effectively drains to the lymph nodes and is internalized by antigen-presenting cells (APCs) through Dectin-1-mediated endocytosis, activating the Syk and Raf1 signaling pathways and leading to upregulated TNFSF15 and OX40L expression to activate APCs. Following immunization, CPBG-Al@OVA activates potent CD8+ T cell and humoral responses to inhibit tumor growth. Notably, mice vaccinated with CPBG-Al@OVA showed extended survival, with more than 70% of the mice surviving for over 50days post-tumor challenge. Moreover, the CPBG-Al nanoparticle also possesses personalized immune-activating capacity by encapsulating tumor lysate as an antigen, specifically suppressing tumor growth. This strategy synergizes the adjuvant effects of aluminum and β-1,3-glucan, offering a platform for self-adjuvanted nanovaccine design with significant clinical translational potential.

DNA-PK inhibition sustains the antitumor innate immune response in Small Cell Lung Cancer

DNA-PK inhibition sustains the antitumor innate immune response in Small Cell Lung Cancer