Immunogenicity of cell death and cancer immunotherapy with immune checkpoint inhibitors

Cellular and Molecular Immunology, Год журнала: 2024, Номер unknown

Опубликована: Дек. 10, 2024

While immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the clinical management of various malignancies, a large fraction patients are refractory to ICIs employed as standalone therapeutics, necessitating development combinatorial treatment strategies. Immunogenic cell death (ICD) inducers have attracted considerable interest partners for ICIs, at least in part owing their ability initiate tumor-targeting adaptive response. However, compared either approach alone, regimens involving ICD and not always shown superior activity. Here, we discuss accumulating evidence on therapeutic interactions between oncological settings, identify key factors that may explain discrepancies preclinical findings, propose strategies address existing challenges increase efficacy these combinations cancer.

Язык: Английский

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Photodynamic Therapy in Cancer: Insights into Cellular and Molecular Pathways

Current Issues in Molecular Biology, Год журнала: 2025, Номер 47(2), С. 69 - 69

Опубликована: Янв. 21, 2025

Photodynamic therapy is a non-ionizing radiation treatment that utilizes photosensitizer in combination with light to produce singlet oxygen. This oxygen induces anti-cancer effects by causing apoptotic, necrotic, or autophagic cell death tumor cells. Currently, photodynamic employed oncology treat various cancers. In the presence of oxygen, this non-invasive approach leads direct death, damage microvasculature, and induction local inflammatory response. These allow be effective treating early-stage tumors, extending survival cases where surgery not feasible, significantly improving quality life. paper, we provide state art on cytomolecular mechanisms associated pathways involved therapy. By integrating these mechanistic insights most recent advancements nanotechnology, phototherapeutic has potential become prevalent option within conventional cancer therapies, enhancing its application precision medicine.

Язык: Английский

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Manganese-pyrochloric acid photosensitizer nanocomplexes against osteosarcoma: achieving both high activatability and high effectiveness

Frontiers in Bioengineering and Biotechnology, Год журнала: 2025, Номер 12

Опубликована: Фев. 11, 2025

The application of photodynamic therapy (PDT) is limited by unsatisfactory therapeutic efficacy and dose-dependent phototoxicity in clinical settings. Intravenous nano-drug delivery systems (NDDSs) hold promise for enhancing the efficiency photosensitive drugs, but often result aggregation-caused quenching (ACQ) effects, preventing site-specific activation. We exploited manganese (Mn2+)-pyrochloric acid (PPa) nanocomplexes coordinated using photosensitizer PPa metal Mn ion treatment osteosarcoma. were precisely co-assembled water to stably co-deliver Mn2+ PPa, enabling tumor-specific release fluorescence recovery. Following laser irradiation, activated significantly enhanced killing effects on primary cancer cells. Additionally, ions cyclic GMP-AMP synthase (cGAS)-stimulator interferon genes (STING) pathway, promoting maturation dendritic cells (DCs) augmenting CD8+-mediated antitumor immune responses. This study advances on-demand activation drugs immunotherapy toward applicability exploiting Mn2+-PPa with high activatability effectiveness targeted PDT immunotherapy.

Язык: Английский

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Fighting Cancer with Photodynamic Therapy and Nanotechnologies: Current Challenges and Future Directions

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(7), С. 2969 - 2969

Опубликована: Март 25, 2025

Photodynamic therapy (PDT) is an innovative treatment that has recently been approved for clinical use and holds promise cancer patients. It offers several benefits, such as low systemic toxicity, minimal invasiveness, the ability to stimulate antitumor immune responses. For certain types of cancer, it shown positive results with few side effects. However, PDT still faces some challenges, including limited light penetration into deeper tumor tissues, uneven distribution photosensitizer (PS) can also affect healthy cells, difficulties posed by hypoxic microenvironment (TME). In conditions, PDT's effectiveness reduced due insufficient production reactive oxygen species, which limits destruction lead relapse. This review highlights recent advances in photosensitizers nanotechnologies are being developed improve PDT. focuses on multifunctional nanoplatforms nanoshuttles have preclinical studies, especially treating solid tumors. One key areas focus development PSs specifically target mitochondria treat deep-seated malignant New mitochondria-targeting nano-PSs designed better water solubility extended wavelength ranges, allowing them tumors more effectively, even challenging, environments. These advancements opening new doors treatment, when combined other therapeutic strategies. Moving forward, research should optimizing PDT, creating efficient drug delivery systems, developing smarter platforms. Ultimately, these efforts aim make a first-choice option

Язык: Английский

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Phototherapy in cancer treatment: strategies and challenges

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Апрель 2, 2025

Abstract Phototherapy has emerged as a promising modality in cancer treatment, garnering considerable attention for its minimal side effects, exceptional spatial selectivity, and optimal preservation of normal tissue function. This innovative approach primarily encompasses three distinct paradigms: Photodynamic Therapy (PDT), Photothermal (PTT), Photoimmunotherapy (PIT). Each these modalities exerts antitumor effects through unique mechanisms—specifically, the generation reactive oxygen species (ROS), heat, immune responses, respectively. However, significant challenges impede advancement clinical application phototherapy. These include inadequate ROS production rates, subpar photothermal conversion efficiency, difficulties tumor targeting, unfavorable physicochemical properties inherent to traditional phototherapeutic agents (PTs). Additionally, hypoxic microenvironment typical tumors complicates therapeutic efficacy due limited agent penetration deep-seated lesions. To address limitations, ongoing research is fervently exploring solutions. The advantages offered by nano-PTs nanocarrier systems aim enhance approaches’ effectiveness. Strategies such generating situ within or inhibiting mitochondrial respiration while targeting HIF-1α pathway may alleviate hypoxia. Moreover, utilizing self-luminescent materials, near-infrared excitation sources, non-photoactivated sensitizers, wireless light delivery can improve penetration. Furthermore, integrating immunoadjuvants modulating immunosuppressive cell populations deploying checkpoint inhibitors holds promise enhancing immunogenic death PIT. review seeks elucidate fundamental principles biological implications phototherapy discussing dominant mechanisms advanced strategies designed overcome existing challenges—ultimately illuminating pathways future aimed at amplifying this intervention’s efficacy.

Язык: Английский

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Targeting pyroptosis for cancer immunotherapy: mechanistic insights and clinical perspectives

Molecular Cancer, Год журнала: 2025, Номер 24(1)

Опубликована: Май 3, 2025

Pyroptosis is a distinct form of programmed cell death characterized by the rupture membrane and robust inflammatory responses. Increasing evidence suggests that pyroptosis significantly affects tumor microenvironment antitumor immunity releasing damage-associated molecular patterns (DAMPs) pro-inflammatory mediators, thereby establishing it as pivotal target in cancer immunotherapy. This review thoroughly explores mechanisms underlying pyroptosis, with particular focus on inflammasome activation gasdermin family proteins (GSDMs). It examines role pyroptotic reshaping immune (TIME) involving both cells, discusses recent advancements targeting pathways through therapeutic strategies such small molecule modulators, engineered nanocarriers, combinatory treatments checkpoint inhibitors. We also advances future directions to enhance immunotherapy inhibitors, adoptive therapy, vaccines. study suggested offers promising avenue amplify responses surmount resistance existing immunotherapies, potentially leading more efficacious treatments.

Язык: Английский

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Integration of Metabolomics and Transcriptomics to Reveal the Antitumor Mechanism of Dendrobium officinale Polysaccharide-Based Nanocarriers in Enhancing Photodynamic Immunotherapy in Colorectal Cancer

Pharmaceutics, Год журнала: 2025, Номер 17(1), С. 97 - 97

Опубликована: Янв. 13, 2025

Background: The mechanism of Dendrobium officinale polysaccharide-based nanocarriers in enhancing photodynamic immunotherapy colorectal cancer (CRC) remains poorly understood. Methods: effects TPA-3BCP-loaded cholesteryl hemisuccinate–Dendrobium polysaccharide nanoparticles (DOP@3BCP NPs) and their potential molecular action a tumor-bearing mouse model CRC were investigated using non-targeted metabolomics transcriptomics. Meanwhile, histopathological analysis (H&E staining, Ki67 TUNEL assay) qRT-PCR revealed the antitumor DOP@3BCP NPs with without light activation. Results: Through transcriptomics analysis, we found an alteration metabolome functional pathways examined tumor tissues. metabolic showed 69 60 differentially expressed metabolites (DEMs) positive- negative-ion modes, respectively, treated samples compared to Control samples. that 1352 genes among three groups. regulated primally related immune response. results pathological histology assay verified findings integrated analysis. Conclusions: Overall, our elucidate mechanisms D. nanocarrier CRC.

Язык: Английский

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Multiple programmed cell death patterns predict the prognosis and drug sensitivity in gastric cancer

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Фев. 4, 2025

Background Gastric cancer (GC) is a malignant tumor with poor prognosis. The diverse patterns of programmed cell death (PCD) are significantly associated the pathogenesis and progression GC, it has potential to serve as prognostic drug sensitivity indicators for GC. Method sequencing data clinical characteristics GC patients were downloaded from Cancer Genome Atlas GEO databases. LASSO cox regression method was used screen feature genes develop PCD score (PCDS). Immune infiltration, immune checkpoint expression, Tumor Dysfunction Exclusion (TIDE) algorithm analysis explore immunotherapy response. By integrating PCDS characteristics, we constructed validated nomogram that demonstrated robust predictive performance. Results We screened nine PCD-related (SERPINE1, PLPPR4, CDO1, MID2, NOX4, DYNC1I1, PDK4, MYB, TUBB2A) create PCDS. found high experienced poorer prognoses, identified an independent factor. Furthermore, there significant difference in profile between low groups. Additionally, indicated may exhibit resistance standard adjuvant chemotherapy regimens; however, they benefit FDA-approved Dasatinib. Conclusion Overall, confirmed risk factor valuable predictor response patients, which provides new evidence application

Язык: Английский

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Honokiol‐Magnolol‐Baicalin Possesses Synergistic Anticancer Potential and Enhances the Efficacy of Anti‐PD‐1 Immunotherapy in Colorectal Cancer by Triggering GSDME‐Dependent Pyroptosis

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Фев. 14, 2025

Abstract Significant progress is made in the treatment of metastatic colorectal cancer (mCRC) patients, however, therapeutic options remain limited for patients with mCRC. In recent years, traditional Chinese medicine (TCM) has gained significant attention. Among these, Huangqin Houpo decoction demonstrated efficacy mCRC treatment. Despite its promise, active ingredients and mechanisms underlying anticancer effects unclear. Using integrative pharmacological approaches, six compounds are identified as primary decoction. them, honokiol (H), magnolol (M), baicalin (B) found to exhibit a synergistic effect on CRC. The HMB combination significantly outperforms mono‐ or bi‐agent treatments reducing tumor growth. Furthermore, surpasses that medium‐ high‐dose FOLFOX regimen. Notably, comparable FOLFOIRI Most importantly, shown enhance sensitivity CRC cells anti‐PD‐1 immunotherapy vivo. Mechanistic studies reveal exerts enhances by inducing GSDME‐dependent pyroptosis. Our study will hopefully provide potential strategy future.

Язык: Английский

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From Inflammasomes to Pyroptosis: Molecular Mechanisms in Chronic Intestinal Diseases — Opportunity or Challenge?

Journal of Inflammation Research, Год журнала: 2025, Номер Volume 18, С. 3349 - 3360

Опубликована: Март 1, 2025

Pyroptosis is a unique form of programmed cell death characterized by intense inflammation. It involves the activation Gasdermin proteins, which membrane pores, leading to rapid rupture and release inflammatory molecules. Unlike other types death, pyroptosis has distinct mechanisms plays complex role in chronic intestinal diseases, including bowel disease, fibrosis, infectious enteritis, colorectal cancer. This review comprehensively examines how influences disease development progression while exploring therapeutic potential targeting pyroptosis-related pathways. Moreover, interplay between gut microbiota summarized, highlighting its critical pathogenesis disorders. A deeper understanding these diseases may provide valuable insights for future research contribute innovative strategies gastroenterology.

Язык: Английский

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