Tumor Treatment Research Articles

Genetic ancestry superpopulations show distinct prevalence and outcomes across pediatric central nervous system tumors from the PBTA and PNOC.

Central nervous system (CNS) tumors lead to cancer-related mortality in children. Genetic ancestry-associated cancer prevalence and outcomes have been studied, but is limited. We performed genetic ancestry prediction in 1,452 pediatric patients with paired normal and tumor whole genome sequencing from the Open Pediatric Cancer (OpenPedCan) project to evaluate the influence of reported race and ethnicity and ancestry-based genetic superpopulations on tumor histology, molecular subtype, survival, and treatment. Predicted superpopulations included African (AFR, N=153), Admixed American (AMR, N=222), East Asian (EAS, N=67), European (EUR, N=968), and South Asian (SAS, N=42). Reported race and ethnicity and ancestry-based genetic superpopulations were non-randomly associated (p<0.001). Patients with an atypical teratoid rhabdoid tumor or meningioma were enriched for AFR ancestry (OR=2.6, FDR=0.01; OR=2.9, FDR=0.01, respectively). Among KIAA1549::BRAF fusion-positive low-grade glioma (LGG) diagnoses, EAS and SAS patients disproportionately harbored exon 15:09 breakpoints (FDR<0.05), and AMR patients demonstrated rare breakpoints, which were associated with lesser degree of surgical resection and worse event free survival (EFS) versus other breakpoints (HR=4.6, p=0.03). Non-EUR and AMR patients with germ cell tumors and SHH-activated medulloblastoma, respectively, exhibited worse EFS relative to EUR patients (HR=12.1, p<0.01; HR=5.2, p=0.03) and AFR patients with LGG (HR=16.4, p<0.01) or ependymoma (HR=5.5, p=0.02) had worse overall survival compared to EUR patients. We observed higher frequency of clinical trial enrollment among AMR patients across tumor histologies (OR=2.0, p=<0.01), but increased utilization of photon versus proton radiation relative to other superpopulations (OR=0.55, p=0.04). Genetic ancestry-associated differences exist across pediatric CNS tumor histological and molecular subtypes from PBTA and PNOC. Further investigation into genetic and socioeconomic factors contributing to these observed inequities is needed.

177Lu-Labeled Heterodimeric Agent with High Stability Targeting Neovascularization for Tumor Radioligand Therapy.

Radiopharmaceutical theranostics holds significant promise in tumor diagnosis and treatment, but suboptimal tumor uptake and retention remain a persistent limitation. We have conjugated a unique albumin binder to our previously developed heterodimeric precursor HX01 and achieved a novel precursor L6, aiming to prolong circulation time and enhance tumor accumulation and retention. However, we observed that the NGR sequence of L6 was gradually rearranged to iso-DGR under alkaline conditions, resulting in decreased stability. In this study, we further modified the L6 to synthesize XH02, subsequently assessing their in vitro and in vivo properties following radiolabeling. Utilizing positron emission tomography (PET)/computed tomography (CT) imaging, single-photon emission computed tomography (SPECT)/CT imaging, and biodistribution study in BxPC-3 xenograft mice, we observed striking accumulation and retention of radiopharmaceutical within tumors. Two cycles of administration of 177Lu-XH02 displayed exceptional tumor growth inhibition in BxPC-3 tumors while causing minimal side effects. This promising result underscores the immense potential of this agent for further clinical translation and investigation.

Hyaluronic acid modified metal-organic frameworks loading cisplatin achieve combined chemodynamic therapy and chemotherapy for lung cancer.

As one of the most commonly used chemotherapeutic agents in clinical practice, cisplatin is unable to selectively accumulate in tumor tissue due to its lack of targeting ability, leading to increased systemic toxicities. Additionally, the effectiveness of monotherapy is greatly limited. Therefore, the development of new cisplatin-based drug delivery systems is essential to improve the effectiveness of tumor treatment. In this study, an iron-based metal-organic framework (MOF) was synthesized to encapsulate cisplatin, and then coated with hyaluronic acid (HA) to create a MOF-based nanoplatform called MPt@HA NPs. This novel nanoplatform achieved the combination of chemodynamic therapy (CDT) with targeted chemotherapy for the treatment of lung cancer. The results showed that MPt@HA NPs have stronger cytotoxicity compared to conventional doses of cisplatin due to the generation of reactive oxygen species (ROS) through the Fenton reaction and DNA damage caused by cisplatin. Therefore, MPt@HA NPs effectively inhibit the tumor growth and prolong the median survival of tumor-bearing mice. Therefore, the MOF-based nanoplatform MPt@HA NPs may present a new option for multi-modal therapy of solid tumors.

Tumor Microenvironment-Driven Structural Transformation of Vanadium-Based MXenzymes to Amplify Oxidative Stress for Multimodal Tumor Therapy.

MXenzymes, a promising class of catalytic therapeutic material, offer great potential for tumor treatment, but they encounter significant obstacles due to suboptimal catalytic efficiency and kinetics in the tumor microenvironment (TME). Herein, this study draws inspiration from the electronic structure of transition metal vanadium, proposing the leverage of TME specific-features to induce structural transformations in sheet-like vanadium carbide MXenzymes (TVMz). These transformations trigger cascading catalytic reactions that amplify oxidative stress, thereby significantly enhancing multimodal tumor therapy. Specifically, the engineered HTVMz, coated with hyaluronic acid, exhibits good stability and generates a thermal effect under NIR-II laser irradiation. The thermal effect, combined with TME characteristics, facilities a structural transformation into ultra-small vanadium oxide nanozymes (VOx). The enlarged surface area of VOx substantially enhances ROS regeneration and amplifies oxidative stress, which promotes lysosomal permeability and induces endoplasmic reticulum stress. The high-valent vanadium in VOx interacts with intracellular glutathione, disrupting redox homeostasis and intensifying oxidative stress further. These amplifications accelerate tumor apoptosis, induce ferroptosis, and suppress HSP90 expression. Consequently, the heightened thermal sensitivity of HTVMz synergistically promotes tumor cell death via multimodal therapeutic pathways. This study presents an innovative strategy for tumor catalytic therapy by manipulating MXenzymes structures, advancing the field of catalytic therapy.

Brassinin from Brassica campestris L. inhibits colorectal cancer by inducing p62/NRF2/GPX4-regulated ferroptosis.

Indole phytoalexins, plant-derived compounds present in cruciferous vegetables, have demonstrated anticancer properties. Brassinin (BSN), derived from Brassica campestris L. var. campestris, is known for its potent antitumor effects on various cancers. However, the role of ferroptosis in regulating the antitumor effects of BSN has not been fully elucidated. The components of B. campestris L. against colorectal cancer (CRC) were analyzed by network pharmacology. CCK-8 assay and colony formation assay detected cell viability induced by BSN. Molecular docking verified the binding of BSN to the target protein. Western blot and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) assay revealed whether BSN can inactivate the NRF2 signaling and inhibit the expression of p62 and HO-1. The RKO-xenograft tumor models were established and then were treated by 75 or 150 mg/kg BSN to verify the antitumor efficacy and side effects of BSN. Network pharmacology suggested that BSN is the most important component of B. campestris L. against CRC. BSN inhibits CRC cell viability in a dose- and time-dependent manner. Furthermore, this inhibitory effect is associated with the induction of ferroptosis, as BSN suppresses the cell viability of CRC by inducing GPX4-regulated ferroptosis. BSN may bind to NRF2 protein to inactivate the NRF2 signaling, inhibiting the expression of p62 and HO-1. Importantly, a low dose or a high dose of BSN significantly reduced the tumor growth invivo. Our findings reveal that BSN blocks CRC growth by inducing p62/NRF2/GPX4-regulated ferroptosis, which may be a novel lead compound for tumor treatment.

MT1JP: A Pivotal Tumor-Suppressing LncRNA and its Role in Cancer Progression and Therapeutic Potential.

Metallothionein 1J pseudogene (MT1JP) is a long non-coding RNA (lncRNA) that functions as a tumor suppressor in various malignancies. Reduced MT1JP expression is associated with increased tumor proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and treatment resistance in nine cancers, such as gastric cancer, intrahepatic cholangiocarcinoma, hepatocellular carcinoma, and breast cancer. Mechanistically, MT1JP acts as a competitive endogenous RNA (ceRNA) to regulate oncogenic microRNAs (miRNAs), including miR-92a-3p, miR-214-3p, and miR-24-3p. This regulation restores tumor suppressor genes, such as FBXW7, RUNX3, and PTEN, thereby disrupting oncogenic pathways, including PI3K/AKT, Wnt/βcatenin, and p53, promoting apoptosis, and inhibiting tumor progression. Clinically, MT1JP expression correlates with tumor grade, differentiation, TNM stage, lymph node metastasis, and patient prognosis, suggesting its potential as a diagnostic and prognostic biomarker. Furthermore, its therapeutic potential in RNA-based treatments has attracted significant attention. Despite these findings, questions remain regarding its role in epigenetic regulation, transcriptional control, and RNA delivery. This review explores the molecular mechanisms underlying MT1JP, highlighting its clinical relevance and potential as a therapeutic target. Future research should focus on elucidating its role in epigenetic regulation, overcoming challenges in therapeutic delivery, and validating its utility as a biomarker for different cancers. MT1JP holds promise for advancing precision oncology by providing innovative approaches for cancer diagnosis and treatment.

Multifunctional Artificial Peroxisome Basing on Lactate Oxidase as a Self-Cascade Enhancing Active Oxygen Amplifier for Tumor Therapy.

The intricacy, diversity, and heterogeneity of cancers make research focus on developing multimodal synergistic therapy strategies. Herein, an oxygen (O2) self-feeding peroxisomal lactate oxidase (LOX)-based LOX-Ce6-Mn (LCM) was synthesized using a biomineralization approach, which was used for cascade chemodynamic therapy (CDT)/photodynamic therapy (PDT) combination therapies through dual depletion of lactate (Lac) and reactive oxygen species (ROS) generation. After endocytosis into tumor cells, the endogenous hydrogen peroxide (H2O2) can be converted to O2 by the catalase-like (CAT) activity of LCM, which can facilitate the catalytic reaction of LOX to consume more Lac and alleviate tumor hypoxia to enhance the generation of singlet oxygen (1O2) upon light irradiation. In addition, the H2O2 produced by LOX catalysis and oxidase-like (OXD) activity of LCM can be catalyzed into highly toxic hydroxyl radicals (•OH) via the Fenton-like reaction, enhancing oxidative damage to tumor cells. Both in vitro and in vivo experiments confirmed that LCM significantly promoted ROS accumulation and effectively inhibited tumor growth by inducing tumor cell autophagy under the combined effect of Lac depletion and CDT with PDT. Therefore, integrally designed LCM for reprogramming metabolism and the tumor microenvironment offers a promising multimodal strategy for tumor treatments.

Multi-pathway oxidative stress amplification via controllably targeted nanomaterials for photoimmunotherapy of tumors

Photoimmunotherapy, which combines phototherapy with immunotherapy, exhibits significantly improved therapeutic effects compared with mono-treatment regimens. However, its use is associated with drawbacks, such as insufficient reactive oxygen species (ROS) production and uneven photosensitizer distribution. To address these issues, we developed a controllable, targeted nanosystem that enhances oxidative stress through multiple pathways, achieving synergistic photothermal, photodynamic, and immunotherapy effects for tumor treatment. These nanoparticles (D/I@HST NPs) accurately target overexpressed transferrin receptors (TfRs) on the surface of tumor cells through surface-modified transferrin (Tf). After endocytosis, D/I@HST NPs generate ROS under 808-nm laser irradiation, breaking the ROS-responsive crosslinking agent and increasing drug release and utilization. Tf also carries Fe3+, which is reduced to Fe2+ by iron reductase in the acidic tumor microenvironment (TME). Consequently, the endoperoxide bridge structure in dihydroartemisinin is cleaved, causing additional ROS generation. Furthermore, the released IR-780 exerts both photodynamic and photothermal effects, enhancing tumor cell death. This multi-pathway oxidative stress amplification and photothermal effect can trigger immunogenic cell death in tumors, promoting the release of relevant antigens and damage-associated molecular patterns, thereby increasing dendritic cell maturation and sensitivity of tumor cells to immunotherapy. Mature dendritic cells transmit signals to T cells, increasing T cells infiltration and activation, facilitating tumor growth inhibition and the suppression of lung metastasis. Furthermore, the myeloid-derived suppressor cells in the tumor decreases significantly after treatment. In summary, this multi-pathway oxidative stress-amplified targeted nanosystem effectively inhibits tumors, reverses the immunosuppressive tumor microenvironment, and provides new insights into tumor immunotherapy combined with phototherapy.

CD133+PD-L1+ cancer cells confer resistance to adoptively transferred engineered macrophage-based therapy in melanoma

Adoptive transfer of genetically or nanoparticle-engineered macrophages represents a promising cell therapy modality for treatment of solid tumor. However, the therapeutic efficacy is suboptimal without achieving a complete tumor regression, and the underlying mechanism remains elusive. Here, we discover a subpopulation of cancer cells with upregulated CD133 and programmed death-ligand 1 in mouse melanoma, resistant to the phagocytosis by the transferred macrophages. Compared to the CD133-PD-L1- cancer cells, the CD133+PD-L1+ cancer cells express higher transforming growth factor-β signaling molecules to foster a resistant tumor niche, that restricts the trafficking of the transferred macrophages by stiffened extracellular matrix, and inhibits their cell-killing capability by immunosuppressive factors. The CD133+PD-L1+ cancer cells exhibit tumorigenic potential. The CD133+PD-L1+ cells are further identified in the clinically metastatic melanoma. Hyperthermia reverses the resistance of CD133+PD-L1+ cancer cells through upregulating the ‘eat me’ signal calreticulin, significantly improving the efficacy of adoptive macrophage therapy. Our findings demonstrate the mechanism of resistance to adoptive macrophage therapy, and provide a de novo strategy to counteract the resistance.

Artificial Intelligence (AI) and Liquid Biopsy Transforming Early Detection of Liver Metastases in Gastrointestinal Cancers.

Liver metastases from Gastrointestinal (GI) cancers present significant challenges in oncology, often signaling poor prognosis. Traditional detection methods like imaging and tissue biopsies have limitations in sensitivity, specificity, and tumor heterogeneity represen-tation. The advent of artificial intelligence (AI) in healthcare, driven by advancements in ma-chine learning, algorithms, and data science, offers a promising frontier for early detection and management of liver metastases. This review explores the integration of AI and liquid biopsy technologies as transformative tools in the proactive detection of liver metastases aris-ing from GI malignancies. Liquid biopsy, a non-invasive method, analyzes circulating tumor cells (CTCs), cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA) in bodily fluids. It provides a compre-hensive overview of tumor heterogeneity and enables real-time monitoring of tumor evolu-tion and treatment response. Despite its advantages, liquid biopsy faces challenges such as low sensitivity for early-stage metastases, reduced detectability due to liver filtration, and technical limitations. AI enhances the potential of liquid biopsies by improving diagnostic accuracy through ad-vanced algorithms like Convolutional Neural Networks (CNNs) and Natural Language Pro-cessing (NLP). These AI models analyze complex biomedical data, offering higher sensitivity and specificity in cancer detection. The synergy between AI and liquid biopsies promises early detection, better disease monitoring, and personalized treatment strategies. This review underscores the significant advancements AI and liquid biopsy technologies bring to oncological precision medicine, particularly in improving overall survival (OS) and disease-free survival (DFS) for patients with GI cancer metastases. As we transition into the era of precision medicine, the integration of these technologies holds the potential to redefine cancer care and patient management.

A powerful organic photosensitizer for effective treatment of malignant tumor via activating antitumor immune response.

Photodynamic therapy (PDT) has emerged as an innovative approach in cancer treatment, effectively inducing tumor cell death through light-triggered reactive oxygen species (ROS) generation. Additionally, PDT can also trigger antitumor immune responses, thereby reducing the risk of postoperative tumor recurrence. However, the development of highly efficient photosensitizers aimed at activating immune responses for comprehensive tumor eradication remains at an early stage. In this study, we developed a new organic photosensitizer, ThC, which exhibits excellent mitochondrial-targeting effect and significantly enhanced ROS production compared to traditional photosensitizers, such as Chlorin e6 (Ce6). Our findings demonstrate that ThC robustly induces immunogenic cell death (ICD) process in hepatic cancer cells, which could effectively transform immunologically "cold" tumors into "hot" tumors. Through in situ injection and subsequent white light irradiation, ThC achieved superior efficacy in eliminating subcutaneous hepatic tumors compared to Ce6 treatment. Immunological analyses revealed that ThC treatment led to elevated levels of CD4+ and CD8+ T cells, along with a reduction in immunosuppressive cell populations (Tregs and tumor-associated macrophages) within the tumor microenvironment. This study provides a novel therapeutic agent with significant potential for clinical translation in the treatment of malignant tumors.

Tumor-nerve interactions in cancer regulation and progression.

Tumor-nerve interactions play a critical role in tumor progression, metastasis, and treatment resistance, redefining our understanding of the tumor microenvironment. This review provides a comprehensive analysis of how the peripheral and central nervous systems contribute to cancer biology, focusing on mechanisms of neural invasion, immune evasion, and tumor adaptation. It has highlighted the emerging potential of repurposing nervous system-targeted drugs originally developed for neurodegenerative and autoimmune diseases as innovative cancer therapies. The review also addresses key challenges, including the limitations of current experimental models and the complexity of translating preclinical findings to clinical applications. By bridging the gap between neuroscience and oncology, this interdisciplinary study aims to discover novel therapeutic strategies to improve outcomes for cancer patients.

Glutathione-scavenging natural-derived ferroptotic nano-amplifiers strengthen tumor therapy through aggravating iron overload and lipid peroxidation.

Nanomedicine-driven ferroptosis has emerged as a promising tumor treatment strategy through delivering exogenous iron and aggravating the lethal accumulation of lipid peroxides (LPO). However, the compensatory mechanisms of ferroptosis defense systems in cancer cells compromise the therapeutic efficacy and lead to potential side effects. Herein, a highly effective ferroptotic nano-amplifier is designed to synergistically promote ferroptosis via increasing intracellular labile iron, exacerbating lipid peroxidation and overcoming the defense system. Briefly, a natural-derived amphiphilic polymer composing of chondroitin sulfate (CS), arachidonic acid (AA) and a redox-sensitive linker, cystamine (CYS) is constructed to self-assemble as a GSH-responsive nanodrug delivery system for loading bioactive ingredient Polyphyllin I (PPI) and ferric ion (Fe3+). This nanodrug (CSAA/Fe@PPI) can scavenge the aberrant intracellular GSH via CYS linker, accompanied with the degradation of CSAA/Fe@PPI and the release of PPI, AA and Fe3+. On one hand, the intracellular labile iron level is significantly elevated due to the exogenous delivery of Fe3+ and PPI-induced ferritinophagy. On the other hand, ROS burst and the supplement of AA initiate and propagate the lipid peroxidation chain reaction. Meanwhile, the depletion of intracellular GSH suppresses the GPX4 activity, further strengthening the lethal accumulation of LPO. Consequently, the ferroptotic antitumor efficacy is remarkably improved by systemically aggravating iron overload and lipid peroxidation. Therefore, our study presents an effective strategy to improve ferroptosis-based anti-cancer treatment through multiple intervention routes.

Inhibition of PDT-induced PGE2 surge for enhanced photo-immunotherapy.

Nowadays, photodynamic therapy (PDT) offers a non-invasive tumor treatment with high safety profiles and minimal side effects, implying a promising clinical application for patients with malignant tumors. However, the lack of efficacy in metastasis and recurrence still notably limits its application. To solve this problem, one promising strategy is to improve the immune response activated by PDT. Unfortunately, tumor cells derived PGE2 could create immunosuppressive microenvironments and impair the function of multiple immune cells, leading to a failure of immune system activation. Moreover, our research revealed the up-regulation of Ptgs2 in tumor cells after the PDT process, which is associated with a series of pro-tumor effects, including proliferation, invasion, metastasis, apoptotic resistance, and immune evasion. Consequently, controlling the PGE2 surge induced by PDT is crucial for optimizing the efficacy of photo-immunotherapy. Therefore, we combined the regulation of the COX2-PGE2 axis with PDT. The addition of COX inhibitors (COX-Is) could improve the efficiency of PDT, reduce the immunosuppressive effect of PGE2, and help dying tumor cells activate the immune system. Herein, a tumor-targeted nano-delivery platform (FI@T-Lipo) was developed using advanced microfluidic technology. FI@T-Lipo based PDT showed a systemic therapeutic effect in triple negative breast cancer through reclaiming the anti-tumor effect of the immune system under COX2-PGE2 blockage. In a word, we developed an in-situ tumor vaccination strategy based on COX-Is enhanced PDT, which could alleviate intra-tumoral immune suppression and boost immune system activation. Our study offers a promising modality for advancing clinical treatment strategies for metastatic malignant tumors.

LDHAα, a lactate dehydrogenase A isoform, promotes glycolysis and tumor progression.

Lactate dehydrogenase A (LDHA) is upregulated in multiple cancer types and contributes to the Warburg effect. Several studies have found that many tumor-related genes have subtypes and play important roles in promoting cancer development. Here, we identified a novel LDHA transcript, which produced a new protein 3 kDa larger than LDHA, which we named LDHAα. We found that multiple cancer cell lines express LDHAα, and ectopic expression of LDHAα led to a higher proliferation and migration rate in vitro. Ectopic expression of LDHAα could also promote tumor cell growth in vivo. Conversely, deletion of LDHAα by CRISPR-sgRNA significantly inhibited the growth of tumor cells. LDHAα was found to be mainly located in the cytoplasm, and overexpression or deletion of LDHAα could significantly affect the glucose uptake and lactate production of tumor cells. Further investigation showed that c-MYC and FOXM1 could markedly modulate the expression of both LDHA and LDHAα, especially c-MYC. We found that a small molecular compound targeting LDHA could also inhibit the enzyme activity of LDHAα. LDHAα, LDHA and c-MYC expression was significantly higher in human acute lymphocytic leukemia and colorectal cancer tissue specimens compared to normal controls. In conclusion, our study identified LDHAα as a subtype of LDHA and highlighted its critical role in tumor metabolism, providing a potential new therapeutic target for tumor diagnosis and treatment.

Synergistic photothermal and chemo-therapeutic platform utilizing Cu2-xSe/PDA/AIPH nanoparticles for targeted tumor eradication.

In this study, we developed an innovative Cu2-xSe/PDA/AIPH nanoparticle platform that combines photothermal therapy and chemotherapy for effective tumor treatment. The Cu2-xSe nanoparticles, known for their strong near-infrared (NIR) absorption, were encapsulated within a polydopamine (PDA) and 2,2'-azobis[2-(2-imidazolin-2-yl)propane] dihydrochloride (AIPH) matrix. Upon NIR irradiation, the platform triggers localized heating and subsequent thermal decomposition of AIPH, releasing ROS to induce significant oxidative damage in tumor cells. In vitro and in vivo experiments demonstrated that Cu2-xSe/PDA/AIPH nanoparticles exhibit excellent biocompatibility, effective photothermal conversion, and potent anticancer efficacy. This multifunctional nanosystem offers a promising approach for enhancing tumor therapy by combining PTT with ROS-mediated chemotherapy.

Targeting Lin28: Insights into Biology and Advances with AI-Driven Drug Development

Lin28, a conserved RNA-binding protein, promotes cancer stem cell features, epithelial-to-mesenchymal transition, and treatment resistance. Lin28 regulates mRNA translation, RNA stability, and transcription, which improve tumor plasticity and treatment resistance, in addition to suppressing let-7 microRNA production. Lin28 is an interesting cancer target due to its many functions; however, its structural complexity makes treatment development difficult. Lin28's proven and new non-canonical activities in cancer biology are examined in this work, focusing on cancer stem cell maintenance, metastasis, and treatment resistance. We highlight computational drug discovery advances targeting Lin28 utilizing virtual screening and machine learning. Generative artificial intelligence has made it easier to develop inhibitors for challenging targets like Lin28. This work integrates current knowledge and technology to demonstrate Lin28's therapeutic potential and outline future techniques to overcome RNA-binding protein targeting challenges.

Activatable Photosensitizer Prodrug for Self-Amplified Immune Therapy via Pyroptosis.

Immunotherapy is a promising cancer treatment, but its application is hindered by tumors' low immunogenicity and the difficulty of immune cell infiltration. Here, to address above issues and achieve targeted tumor treatment, we designed the first activated small molecule photosensitizer immune-prodrug HDIM based on pyroptosis, and proposed a self-amplified immune therapy strategy (SITS) for enhanced tumor therapy. HDIMcan be specifically activated by the tumor hypoxiaand then simultaneously initiate immuno-therapy and photodynamic therapy (PDT)-induced pyroptosis with NIR laser irradiation. Mechanism study demonstrated that the immunogenicity in tumor can be significantly enhanced by HDIM-induced pyroptosis and immune cells are recruited, thus effectively amplifying the therapeutic effect of the released immune drugs. As proof of application, we have utilized HDIM for primary tumor and distant tumor therapy. And the experiment results showed that compared to current monotherapy as well as simple combination therapy, the photosensitizer prodrug HDIM exhibited much superior tumor treatment effect owing to its synchronous activation of pyroptosis and immuno-therapy in tumor.

Anticancer effects of OSW-1 on colorectal cancer cells via the ROS/NLRP3/Caspase-1 pyroptosis signaling pathway.

Pyroptosis, a form of programmed cell death, has recently emerged as a compelling molecular mechanism associated with the efficacy of chemotherapeutic drugs in tumor treatment. OSW-1, derived from the bulbs of Ornithogalum saundersiae Baker, exhibits a diverse range of pharmacological effects. However, its specific antitumor effects on colorectal cancer (CRC) and the mechanisms underlying these effects remain elusive. In this study, we explored whether OSW-1 can induce pyroptosis in CRC cells, aiming to expand its potential clinical applications. Various functional experiments, including Cell Counting Kit-8 (CCK-8), plate colony formation, wound healing, and Transwell assays, were conducted to assess cell proliferation, migration, and invasion. The results of in vitro experiments revealed apparent inhibitory effects of OSW-1 on CRC cells, and we observed a pyroptosis-like morphology in treated cells by scanning electron microscopy (SEM). OSW-1 was found to induce pyroptosis through the NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/cysteinyl aspartate specific proteinase-1 (Caspase-1) pathway, with the production of reactive oxygen species (ROS) mediating this pyroptotic pathway. The results from xenograft animal models further demonstrated that OSW-1 facilitated pyroptosis in CRC cells, significantly inhibiting tumor growth. In summary, our findings suggest that OSW-1 activates pyroptosis in CRC cells through the ROS/NLRP3/Caspase-1 pathway. These results provide valuable evidence regarding the role of pyroptosis in various tumor types, emphasizing the potential of OSW-1 as a therapeutic agent in tumor treatment.

Divergent Crosstalk Between Microglia and T Cells in Brain Cancers: Implications for Novel Therapeutic Strategies.

Background: Brain cancers represent a formidable oncological challenge characterized by their aggressive nature and resistance to conventional therapeutic interventions. The tumor microenvironment has emerged as a critical determinant of tumor progression and treatment efficacy. Within this complex ecosystem, microglia and macrophages play fundamental roles, forming intricate networks with peripheral immune cell populations, particularly T cells. The precise mechanisms underlying microglial interactions with T cells and their contributions to immunosuppression remain incompletely understood. Methods: This review comprehensively examines the complex cellular dialogue between microglia and T cells in two prominent brain malignancies: primary glioblastoma and secondary brain metastases. Results: Through a comprehensive review of the current scientific literature, we explore the nuanced mechanisms through which microglial-T cell interactions modulate tumor growth and immune responses. Conclusions: Our analysis seeks to unravel the cellular communication pathways that potentially underpin tumor progression, with the ultimate goal of illuminating novel therapeutic strategies for brain cancer intervention.