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1.
Phytomedicine ; 129: 155608, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38642413

RESUMEN

BACKGROUND: Despite significant advances in cancer immunotherapy over the past decades, such as T cell-engaging chimeric antigen receptor (CAR)-T cell therapy and immune checkpoint blockade (ICB), therapeutic failure resulting from various factors remains prevalent. Therefore, developing combinational immunotherapeutic strategies is of great significance for improving the clinical outcome of cancer immunotherapy. Natural products are substances that naturally exist in various living organisms with multiple pharmacological or biological activities, and some of them have been found to have anti-tumor potential. Notably, emerging evidences have suggested that several natural compounds may boost the anti-tumor effects through activating immune response of hosts, in which CD8+ T cells play a pivotal role. METHODS: The data of this review come from PubMed, Web of Science, Google Scholar, and ClinicalTrials (https://clinicaltrials.gov/) with the keywords "CD8+ T cell", "anti-tumor", "immunity", "signal 1", "signal 2", "signal 3", "natural products", "T cell receptor (TCR)", "co-stimulation", "co-inhibition", "immune checkpoint", "inflammatory cytokine", "hesperidin", "ginsenoside", "quercetin", "curcumin", "apigenin", "dendrobium officinale polysaccharides (DOPS)", "luteolin", "shikonin", "licochalcone A", "erianin", "resveratrol", "procyanidin", "berberine", "usnic acid", "naringenin", "6-gingerol", "ganoderma lucidum polysaccharide (GL-PS)", "neem leaf glycoprotein (NLGP)", "paclitaxel", "source", "pharmacological activities", and "toxicity". These literatures were published between 1993 and 2023. RESULTS: Natural products have considerable advantages as anti-tumor drugs based on the various species, wide distribution, low price, and few side effects. This review summarized the effects and mechanisms of some natural products that exhibit anti-tumor effects via targeting CD8+ T cells, mainly focused on the three signals that activate CD8+ T cells: TCR, co-stimulation, and inflammatory cytokines. CONCLUSION: Clarifying the role and underlying mechanism of natural products in cancer immunotherapy may provide more options for combinational treatment strategies and benefit cancer therapy, to shed light on identifying potential natural compounds for improving the clinical outcome in cancer immunotherapy.


Asunto(s)
Productos Biológicos , Linfocitos T CD8-positivos , Neoplasias , Humanos , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Animales , Inmunoterapia/métodos
2.
Adv Drug Deliv Rev ; 209: 115306, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38626859

RESUMEN

Cancer immunotherapy represents a revolutionary strategy, leveraging the patient's immune system to inhibit tumor growth and alleviate the immunosuppressive effects of the tumor microenvironment (TME). The recent emergence of immune checkpoint blockade (ICB) therapies, particularly following the first approval of cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors like ipilimumab, has led to significant growth in cancer immunotherapy. The extensive explorations on diverse immune checkpoint antibodies have broadened the therapeutic scope for various malignancies. However, the clinical response to these antibody-based ICB therapies remains limited, with less than 15% responsiveness and notable adverse effects in some patients. This review introduces the emerging strategies to overcome current limitations of antibody-based ICB therapies, mainly focusing on the development of small interfering ribonucleic acid (siRNA)-based ICB therapies and innovative delivery systems. We firstly highlight the diverse target immune checkpoint genes for siRNA-based ICB therapies, incorporating silencing of multiple genes to boost anti-tumor immune responses. Subsequently, we discuss improvements in siRNA delivery systems, enhanced by various nanocarriers, aimed at overcoming siRNA's clinical challenges such as vulnerability to enzymatic degradation, inadequate pharmacokinetics, and possible unintended target interactions. Additionally, the review presents various combination therapies that integrate chemotherapy, phototherapy, stimulatory checkpoints, ICB antibodies, and cancer vaccines. The important point is that when used in combination with siRNA-based ICB therapy, the synergistic effect of traditional therapies is strengthened, improving host immune surveillance and therapeutic outcomes. Conclusively, we discuss the insights into innovative and effective cancer immunotherapeutic strategies based on RNA interference (RNAi) technology utilizing siRNA and nanocarriers as a novel approach in ICB cancer immunotherapy.


Asunto(s)
Silenciador del Gen , Inhibidores de Puntos de Control Inmunológico , Inmunoterapia , Neoplasias , ARN Interferente Pequeño , Humanos , ARN Interferente Pequeño/administración & dosificación , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Inmunoterapia/métodos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Animales , Microambiente Tumoral/inmunología
3.
Int J Pharm ; 656: 124045, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38561134

RESUMEN

The field of cancer therapy is witnessing the emergence of immunotherapy, an innovative approach that activates the body own immune system to combat cancer. Immunogenic cell death (ICD) has emerged as a prominent research focus in the field of cancer immunotherapy, attracting significant attention in recent years. The activation of ICD can induce the release of damage-associated molecular patterns (DAMPs), such as calreticulin (CRT), adenosine triphosphate (ATP), high mobility group box protein 1 (HMGB1), and heat shock proteins (HSP). Subsequently, this process promotes the maturation of innate immune cells, including dendritic cells (DCs), thereby triggering a T cell-mediated anti-tumor immune response. The activation of the ICD ultimately leads to the development of long-lasting immune responses against tumors. Studies have demonstrated that partial therapeutic approaches, such as chemotherapy with doxorubicin, specific forms of radiotherapy, and phototherapy, can induce the generation of ICD. The main focus of this article is to discuss and review the therapeutic methods triggered by nanoparticles for ICD, while briefly outlining their anti-tumor mechanism. The objective is to provide a comprehensive reference for the widespread application of ICD.


Asunto(s)
Muerte Celular Inmunogénica , Inmunoterapia , Nanopartículas , Neoplasias , Humanos , Muerte Celular Inmunogénica/efectos de los fármacos , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Inmunoterapia/métodos , Animales , Nanopartículas/administración & dosificación , Células Dendríticas/inmunología , Células Dendríticas/efectos de los fármacos
4.
J Mater Chem B ; 12(19): 4629-4641, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38666407

RESUMEN

Enlightened by the great success of the drug repurposing strategy in the pharmaceutical industry, in the current study, material repurposing is proposed where the performance of carbonyl iron powder (CIP), a nutritional intervention agent of iron supplement approved by the US FDA for iron deficiency anemia in clinic, was explored in anti-cancer treatment. Besides the abnormal iron metabolic characteristics of tumors, serving as potential targets for CIP-based cancer therapy under the repurposing paradigm, the efficacy of CIP as a catalyst in the Fenton reaction, activator for dihydroartemisinin (DHA), thus increasing the chemo-sensitivity of tumors, as well as a potent agent for NIR-II photothermal therapy (PTT) was fully evaluated in an injectable alginate hydrogel form. The CIP-ALG gel caused a rapid temperature rise in the tumor site under NIR-II laser irradiation, leading to complete ablation in the primary tumor. Further, this photothermal-ablation led to the significant release of ATP, and in the bilateral tumor model, both primary tumor ablation and inhibition of secondary tumor were observed simultaneously under the synergistic tumor treatment of nutritional-photothermal therapy (NT/PTT). Thus, material repurposing was confirmed by our pioneering trial and CIP-ALG-meditated NT/PTT/immunotherapy provides a new choice for safe and efficient tumor therapy.


Asunto(s)
Adenosina Trifosfato , Antineoplásicos , Rayos Infrarrojos , Animales , Adenosina Trifosfato/metabolismo , Adenosina Trifosfato/química , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Inmunoterapia , Reposicionamiento de Medicamentos , Humanos , Rayos Láser , Terapia Fototérmica , Ratones Endogámicos BALB C , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Alginatos/química , Femenino , Hidrogeles/química , Hidrogeles/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Tamaño de la Partícula , Artemisininas/química , Artemisininas/farmacología
5.
Crit Rev Oncol Hematol ; 198: 104359, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38615871

RESUMEN

Ferroptosis is an unconventional programmed cell death mode caused by phospholipid peroxidation dependent on iron. Emerging immunotherapies (especially immune checkpoint inhibitors) have the potential to enhance lung cancer patients' long-term survival. Although immunotherapy has yielded significant positive applications in some patients, there are still many mechanisms that can cause lung cancer cells to evade immunity, thus leading to the failure of targeted therapies. Immune-tolerant cancer cells are insensitive to conventional death pathways such as apoptosis and necrosis, whereas mesenchymal and metastasis-prone cancer cells are particularly vulnerable to ferroptosis, which plays a vital role in mediating immune tolerance resistance by tumors and immune cells. As a result, triggering lung cancer cell ferroptosis holds significant therapeutic potential for drug-resistant malignancies. Here, we summarize the mechanisms underlying the suppression of ferroptosis in lung cancer, highlight its function in the lung cancer immune microenvironment, and propose possible therapeutic strategies.


Asunto(s)
Ferroptosis , Inmunoterapia , Neoplasias Pulmonares , Microambiente Tumoral , Ferroptosis/efectos de los fármacos , Ferroptosis/inmunología , Humanos , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/patología , Inmunoterapia/métodos , Microambiente Tumoral/inmunología , Microambiente Tumoral/efectos de los fármacos , Animales
6.
J Mater Chem B ; 12(17): 4097-4117, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38587869

RESUMEN

Single phototherapy and immunotherapy have individually made great achievements in tumor treatment. However, monotherapy has difficulty in balancing accuracy and efficiency. Combining phototherapy with immunotherapy can realize the growth inhibition of distal metastatic tumors and enable the remote monitoring of tumor treatment. The development of nanomaterials with photo-responsiveness and anti-tumor immunity activation ability is crucial for achieving photo-immunotherapy. As immune adjuvants, photosensitizers and photothermal agents, manganese-based nanoparticles (Mn-based NPs) have become a research hotspot owing to their multiple ways of anti-tumor immunity regulation, photothermal conversion and multimodal imaging. However, systematic studies on the synergistic photo-immunotherapy applications of Mn-based NPs are still limited; especially, the green synthesis and mechanism of Mn-based NPs applied in immunotherapy are rarely comprehensively discussed. In this review, the synthesis strategies and function of Mn-based NPs in immunotherapy are first introduced. Next, the different mechanisms and leading applications of Mn-based NPs in immunotherapy are reviewed. In addition, the advantages of Mn-based NPs in synergistic photo-immunotherapy are highlighted. Finally, the challenges and research focus of Mn-based NPs in combination therapy are discussed, which might provide guidance for future personalized cancer therapy.


Asunto(s)
Inmunoterapia , Manganeso , Humanos , Manganeso/química , Manganeso/farmacología , Inmunoterapia/métodos , Fototerapia/métodos , Tecnología Química Verde , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Animales , Nanoestructuras/química , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/síntesis química , Antineoplásicos/química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Tamaño de la Partícula
7.
J Nanobiotechnology ; 22(1): 192, 2024 Apr 18.
Artículo en Inglés | MEDLINE | ID: mdl-38637848

RESUMEN

Androgen deprivation therapy (ADT) is a crucial and effective strategy for prostate cancer, while systemic administration may cause profound side effects on normal tissues. More importantly, the ADT can easily lead to resistance by involving the activation of NF-κB signaling pathway and high infiltration of M2 macrophages in tumor microenvironment (TME). Herein, we developed a biomimetic nanotherapeutic platform by deriving cell membrane nanovesicles from cancer cells and probiotics to yield the hybrid cellular nanovesicles (hNVs), loading flutamide (Flu) into the resulting hNVs, and finally modifying the hNVs@Flu with Epigallocatechin-3-gallate (EGCG). In this nanotherapeutic platform, the hNVs significantly improved the accumulation of hNVs@Flu-EGCG in tumor sites and reprogramed immunosuppressive M2 macrophages into antitumorigenic M1 macrophages, the Flu acted on androgen receptors and inhibited tumor proliferation, and the EGCG promoted apoptosis of prostate cancer cells by inhibiting the NF-κB pathway, thus synergistically stimulating the antitumor immunity and reducing the side effects and resistance of ADT. In a prostate cancer mouse model, the hNVs@Flu-EGCG significantly extended the lifespan of mice with tumors and led to an 81.78% reduction in tumor growth compared with the untreated group. Overall, the hNVs@Flu-EGCG are safe, modifiable, and effective, thus offering a promising platform for effective therapeutics of prostate cancer.


Asunto(s)
FN-kappa B , Neoplasias de la Próstata , Humanos , Masculino , Animales , Ratones , FN-kappa B/metabolismo , Andrógenos/uso terapéutico , Antagonistas de Andrógenos/farmacología , Antagonistas de Andrógenos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Inmunoterapia/métodos , , Línea Celular Tumoral , Microambiente Tumoral
8.
Methods Mol Biol ; 2782: 147-157, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38622399

RESUMEN

Immunotherapies represent one of the current most promising challenges in cancer treatment. They are based on the boost of natural immune responses, aimed at cancer eradication. However, the success of immunotherapeutic approaches strictly depends on the interaction between immune cells and cancer cells. Preclinical drug tests currently available are poor in fully predicting the actual safety and efficacy of immunotherapeutic treatments under development. Indeed, conventional 2D cell culture underrepresents the complexity of the tumour microenvironment, while in vivo animal models lack in mimicking the human immune cell responses. In this context, predictability, reliability, and complete immune compatibility still represent challenges to overcome. For this aim, novel 3D, fully humanized in vitro cancer tissue models have been recently optimized by adopting emerging technologies, such as organ-on-chips (OOC) and 3D cancer cell-laden hydrogels. In particular, a novel multi-in vitro organ (MIVO) OOC platform has been recently adopted to culture 3D clinically relevant size cancer tissues under proper physiological culture conditions to investigate anti-cancer treatments and immune-tumour cell crosstalk.The proposed immune-tumour OOC-based model offers a potential tool for accurately modelling human immune-related diseases and effectively assessing immunotherapy efficacy, finally offering promising experimental approaches for personalized medicine.


Asunto(s)
Neoplasias , Animales , Humanos , Evaluación Preclínica de Medicamentos , Reproducibilidad de los Resultados , Neoplasias/terapia , Técnicas de Cultivo de Célula , Microambiente Tumoral , Inmunoterapia
9.
ACS Nano ; 18(15): 10439-10453, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38567994

RESUMEN

The cGAS-STING pathway plays a crucial role in innate immune activation against cancer and infections, and STING agonists based on cyclic dinucleotides (CDN) have garnered attention for their potential use in cancer immunotherapy and vaccines. However, the limited drug-like properties of CDN necessitate an efficient delivery system to the immune system. To address these challenges, we developed an immunostimulatory delivery system for STING agonists. Here, we have examined aqueous coordination interactions between CDN and metal ions and report that CDN mixed with Zn2+ and Mn2+ formed distinctive crystal structures. Further pharmaceutical engineering led to the development of a functional coordination nanoparticle, termed the Zinc-Mn-CDN Particle (ZMCP), produced by a simple aqueous one-pot synthesis. Local or systemic administration of ZMCP exerted robust antitumor efficacy in mice. Importantly, recombinant protein antigens from SARS-CoV-2 can be simply loaded during the aqueous one-pot synthesis. The resulting ZMCP antigens elicited strong cellular and humoral immune responses that neutralized SARS-CoV-2, highlighting ZMCP as a self-adjuvant vaccine platform against COVID-19 and other infectious pathogens. Overall, this work establishes a paradigm for developing translational coordination nanomedicine based on drug-metal ion coordination and broadens the applicability of coordination medicine for the delivery of proteins and other biologics.


Asunto(s)
Nanopartículas , Neoplasias , Vacunas , Animales , Ratones , Neoplasias/terapia , Adyuvantes Inmunológicos , Inmunoterapia/métodos , Nanopartículas/química
10.
Clin. transl. oncol. (Print) ; 26(4): 891-904, Abr. 2024. ilus
Artículo en Inglés | IBECS | ID: ibc-VR-52

RESUMEN

Background: Recently, enhancer RNAs (eRNAs) have garnered attention as pivotal biomarkers for the onset and progression of cancer. However, the landscape of eRNAs and the implications of eRNA-based molecular subtypes in stage II/III colorectal cancer (CRC) remain largely unexplored. Methods: Comprehensive profiling of eRNAs was conducted on a public stage II/III CRC cohort with total RNA-seq data. We used unsupervised clustering of prognostic eRNAs to establish an eRNA-based subtyping system. Further evaluations included molecular characteristics, immune infiltration, clinical outcomes, and drug responses. Finally, we validated the eRNA-based subtyping system in The Cancer Genome Atlas (TCGA) CRC cohort. Results: We identified a total of 6453 expressed eRNAs, among which 237 were prognostic. A global upregulation of eRNAs was observed in microsatellite-stable (MSS) CRCs when compared to microsatellite instability-high (MSI-H) CRCs. Through consensus clustering, two novel molecular subtypes, termed Cluster 1(C1) and Cluster 2(C2), were further identified. C1, associated with the activation of epithelial–mesenchymal transition (EMT), hypoxia, and KRAS signaling pathways, showed poorer prognosis. C2, correlated with the canonical CRC subtype, exhibited superior survival outcomes. In addition, C1 showed enrichment with immune infiltration and more sensitivity to immune checkpoint inhibitors. Conclusion: Our study unravels the molecular heterogeneity of stage II/III CRC at the eRNA level and highlights the potential applications of the novel eRNA-based subtyping system in predicting prognosis and guiding immunotherapy.(AU)


Asunto(s)
Humanos , Masculino , Femenino , Inmunoterapia , Pronóstico , Heterogeneidad Genética , Inestabilidad de Microsatélites , Neoplasias Colorrectales/terapia
11.
J Nanobiotechnology ; 22(1): 151, 2024 Apr 04.
Artículo en Inglés | MEDLINE | ID: mdl-38575943

RESUMEN

BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.


Asunto(s)
Neoplasias Óseas , Nanopartículas , Neoplasias , Osteosarcoma , Niño , Humanos , Adolescente , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética , Osteosarcoma/diagnóstico por imagen , Osteosarcoma/terapia , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/tratamiento farmacológico , Inmunoterapia , Línea Celular Tumoral , Fototerapia
12.
Molecules ; 29(7)2024 Apr 08.
Artículo en Inglés | MEDLINE | ID: mdl-38611962

RESUMEN

Phytocompounds have been evaluated for their anti-glioblastoma actions for decades, with promising results from preclinical studies but only limited translation into clinics. Indeed, by targeting multiple signaling pathways deregulated in cancer, they often show high efficacy in the in vitro studies, but their poor bioavailability, low tumor accumulation, and rapid clearance compromise their efficacy in vivo. Here, we present the new avenues in phytocompound research for the improvement of glioblastoma therapy, including the ways to enhance the response to temozolomide using phytochemicals, the current focus on phytocompound-based immunotherapy, or the use of phytocompounds as photosensitizers in photodynamic therapy. Moreover, we present new, intensively evaluated approaches, such as chemical modifications of phytochemicals or encapsulation into numerous types of nanoformulations, to improve their bioavailability and delivery to the brain. Finally, we present the clinical trials evaluating the role of phytocompounds or phytocompound-derived drugs in glioblastoma therapy and the less studied phytocompounds or plant extracts that have only recently been found to possess promising anti-glioblastoma properties. Overall, recent advancements in phytocompound research are encouraging; however, only with more 3D glioblastoma models, in vivo studies, and clinical trials it is possible to upgrade the role of phytocompounds in glioblastoma treatment to a satisfactory level.


Asunto(s)
Glioblastoma , Fotoquimioterapia , Humanos , Glioblastoma/tratamiento farmacológico , Encéfalo , Temozolomida , Inmunoterapia
13.
Int J Mol Sci ; 25(7)2024 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-38612911

RESUMEN

Cancer stem cells (CSCs) represent a subpopulation within tumors that promote cancer progression, metastasis, and recurrence due to their self-renewal capacity and resistance to conventional therapies. CSC-specific markers and signaling pathways highly active in CSCs have emerged as a promising strategy for improving patient outcomes. This review provides a comprehensive overview of the therapeutic targets associated with CSCs of solid tumors across various cancer types, including key molecular markers aldehyde dehydrogenases, CD44, epithelial cellular adhesion molecule, and CD133 and signaling pathways such as Wnt/ß-catenin, Notch, and Sonic Hedgehog. We discuss a wide array of therapeutic modalities ranging from targeted antibodies, small molecule inhibitors, and near-infrared photoimmunotherapy to advanced genetic approaches like RNA interference, CRISPR/Cas9 technology, aptamers, antisense oligonucleotides, chimeric antigen receptor (CAR) T cells, CAR natural killer cells, bispecific T cell engagers, immunotoxins, drug-antibody conjugates, therapeutic peptides, and dendritic cell vaccines. This review spans developments from preclinical investigations to ongoing clinical trials, highlighting the innovative targeting strategies that have been informed by CSC-associated pathways and molecules to overcome therapeutic resistance. We aim to provide insights into the potential of these therapies to revolutionize cancer treatment, underscoring the critical need for a multi-faceted approach in the battle against cancer. This comprehensive analysis demonstrates how advances made in the CSC field have informed significant developments in novel targeted therapeutic approaches, with the ultimate goal of achieving more effective and durable responses in cancer patients.


Asunto(s)
Proteínas Hedgehog , Neoplasias , Humanos , Neoplasias/terapia , Inmunoterapia , Células Madre Neoplásicas , Fototerapia
14.
J Nanobiotechnology ; 22(1): 163, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38600506

RESUMEN

Photothermal immunotherapy is regarded as the ideal cancer therapeutic modality to against malignant solid tumors; however, its therapeutic benefits are often modest and require improvement. In this study, a thermoresponsive nanoparticle (BTN@LND) composed of a photothermal agent (PTA) and pyroptosis inducer (lonidamine) were developed to enhance immunotherapy applications. Specifically, our "two-step" donor engineering strategy produced the strong NIR-II-absorbing organic small-molecule PTA (BTN) that exhibited high NIR-II photothermal performance (ε1064 = 1.51 × 104 M-1 cm-1, η = 75.8%), and this facilitates the diagnosis and treatment of deep tumor tissue. Moreover, the fabricated thermally responsive lipid nanoplatform based on BTN efficiently delivered lonidamine to the tumor site and achieved spatiotemporal release triggered by the NIR-II photothermal effect. In vitro and in vivo experiments demonstrated that the NIR-II photothermal therapy (PTT)-mediated on-demand release of cargo effectively faciliated tumor cell pyroptosis, thereby intensifying the immunogenic cell death (ICD) process to promote antitumor immunotherapy. As a result, this intelligent component bearing photothermal and chemotherapy can maximally suppress the growth of tumors, thus providing a promising approach for pyroptosis/NIR-II PTT synergistic therapy against tumors.


Asunto(s)
Indazoles , Nanopartículas , Neoplasias , Humanos , Fototerapia , Piroptosis , Neoplasias/tratamiento farmacológico , Inmunoterapia , Línea Celular Tumoral
15.
Front Immunol ; 15: 1366489, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660314

RESUMEN

Cancer ranks among the foremost causes of mortality worldwide, posing a significant threat to human lives. The advent of tumor immunotherapy has substantially transformed the therapeutic landscape for numerous advanced malignancies, notably non-small cell lung cancer and melanoma. However, as immune checkpoint inhibitors (ICIs) are increasingly applied in clinical settings, a spectrum of undesired reactions, termed immune-related adverse events (irAEs), has emerged. These adverse reactions are associated with immunotherapy and can result in varying degrees of harm to the human body. Among these reactions, Immune checkpoint inhibitor-induced colitis (ICIIC) stands out as one of the most prevalent clinical adverse events. In contemporary times, traditional Chinese medicine (TCM) has demonstrated remarkable efficacy in addressing various maladies. Consequently, investigating the potential application and mechanisms of Chinese medicine in countering immune checkpoint inhibitor-induced colitis assumes significant importance in the treatment of this condition.


Asunto(s)
Colitis , Inhibidores de Puntos de Control Inmunológico , Medicina Tradicional China , Humanos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Colitis/inducido químicamente , Colitis/inmunología , Colitis/terapia , Animales , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Inmunoterapia/efectos adversos , Inmunoterapia/métodos
16.
Altern Ther Health Med ; 30(4): 130-138, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38518167

RESUMEN

Objective: The emergence of immunotherapy has heralded a profound transformation in the therapeutic landscape of bladder cancer (BLAC). Immunotherapy, with its unique potential for "combination therapy", has brought about greater possibilities for treating BLCA. However, there is significant heterogeneity among bladder cancer patients, and a portion of those in advanced stages may not experience substantial benefits from chemotherapy. Immunotherapy offers a potential ray of hope for specific patient subsets. Thus, predicting the effectiveness of tumor immunotherapy and providing them with more precise treatment strategies hold paramount importance and clinical value in delivering personalized therapeutic interventions for advanced bladder cancer patients. This study is designed to establish a risk score model derived from immune-related genes that can effectively assess prognosis and immunotherapy outcomes in patients with bladder cancer. Methods: The IMvigor210 dataset served as our training set for developing the prognostic model based on immune-related genes. Robust 7-gene expression patterns were investigated from the training set. A time-dependent receiver operating characteristic (ROC) curve and Kaplan-Meier (KM)analysis were employed to determine the prognostic relevance of these gene patterns. Independent datasets collected from the Cancer Genome Atlas Program (TCGA) and Gene Expression Omnibus (GEO) databases were additionally utilized for re-determination. The association between the 7-gene signature-based risk score and immunological subtypes, tumor mutational burden (TMB), immune checkpoint expressions, and the proportion of immune cell infiltration was assessed within training and test sets. Furthermore, the training set's predictive potential for immunotherapy response was assessed using the 7-gene signature, and its validity was externally verified on three datasets (GSE176307, GSE140901, and GSE91016). By validating the 7-gene signature externally, we eneralized the findings beyond the original training set, and assessed the model's performance in diverse contexts. Consistent performance across these datasets reinforces the robustness and clinical utility of our 7-gene signature. Results: Employing the transcriptional and clinical information from the IMvigor210 for training, 348 patients were classified into two clusters with notable distinctions in prognostic stratification and immunotherapy efficacy. Seven immune-related genes Indoleamine 2,3-dioxygenase 1 (IDO1), TNF receptor superfamily member 17 (TNFRSF17), Killer Cell Lectin Like Receptor K1 (KLRK1), TNF receptor superfamily member 14 (TNFSF14), Lymphocyte-activation gene 3 (LAG3), Killer Cell Lectin Like Receptor C1 (KLRC1), and Ecto-5'-nucleotidase (NT5E) were screened based on different expression genes (DEGs) between the two clusters. The expression levels of these seven genes and the accompanying univariate component Cox regression coefficients, were computed to create a 7-gene signature-based risk score. The median value of the risk score was utilized to categorize the BLCA individuals into high-risk and low-risk groups. Researchers identified that in the low-risk group, individuals exhibited a noticeably improved chance of surviving. The external validation cohorts verified the risk score model's prognostic capacity. Furthermore, it was demonstrated that while low-risk individuals possessed higher TMB scores, higher expression of immune checkpoint genes, and lower levels of immunological infiltration, they responded more favorably to immunotherapy. The clinical relevance of the risk score model was validated in three immunotherapy groups. Conclusion: The risk score model might be utilized to forecast the prognosis and efficacy of immunotherapy in BLCA patients, offering a novel course of treatment for these individuals. For patients undergoing immunotherapy, this gene signature can help predict treatment response. Low-risk patients may benefit from more tailored monitoring and personalized immunotherapy regimens. However, more investigations are required to validate its accuracy and effectiveness in a prospective cohort with larger sample sizes.


Asunto(s)
Inmunoterapia , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/terapia , Humanos , Pronóstico , Inmunoterapia/métodos , Biomarcadores de Tumor/genética , Femenino , Masculino
17.
Nanomedicine (Lond) ; 19(10): 841-854, 2024 04.
Artículo en Inglés | MEDLINE | ID: mdl-38436253

RESUMEN

Aims: Preparation and evaluation of nanoparticles for tumor chemotherapy and immunotherapy mild photothermal therapy and oxaliplatin. Methods: The double emulsion method was used for nanoparticle preparations. Polydopamine was deposited on the surface, which was further modified with folic acid. Cytotoxicity assays were carried out by cell counting kit-8. In vivo antitumor assays were carried out on 4T1 tumor-bearing mice. Results: The nanoparticles exhibited a 190 nm-diameter pomegranate-like sphere, which could increase temperature to 43-46°C. In vivo distribution showed enhanced accumulation. The nanoparticles generated stronger immunogenic cell death effects. By stimulating the maturation of dendritic cells, mild photothermal therapy combined with oxaliplatin significantly increased the antitumor effect by a direct killing effect and activation of immunotherapy. Conclusion: This study provided a promising strategy of combination therapy for tumors.


Asunto(s)
Hipertermia Inducida , Nanopartículas , Neoplasias , Animales , Ratones , Oxaliplatino/uso terapéutico , Terapia Fototérmica , Fototerapia/métodos , Neoplasias/tratamiento farmacológico , Inmunoterapia , Línea Celular Tumoral
18.
Dis Colon Rectum ; 67(6): 762-771, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38479009

RESUMEN

BACKGROUND: In April 2023, the National Comprehensive Cancer Network endorsed neoadjuvant immunotherapy for select patients with nonmetastatic mismatch repair deficient colon cancer. Approximately 15% of incident colon cancers are mismatch repair deficient, resulting in a distinct molecular subtype with high microsatellite instability that is responsive to immune checkpoint inhibition. OBJECTIVE: To describe the existing evidence supporting neoadjuvant immunotherapy for mismatch repair deficient, microsatellite unstable nonmetastatic colon cancer. DATA SOURCES: A medical librarian performed PubMed, Embase, and Web of Science searches most recently on April 24, 2023. The PubMed search was re-run on September 26, 2023, to identify any additional studies published between April 24 and September 26, 2023. STUDY SELECTION: Two authors screened titles and abstracts in the published studies. The inclusion criteria were 1) English language, 2) adults with primary cancer of the colon, 3) nonmetastatic disease, 4) neoadjuvant immunotherapy, and 5) reporting on 10 or more cases. INTERVENTION: Neoadjuvant immunotherapy. MAIN OUTCOME MEASURES: Safety (grade 3+ treatment-related adverse events) and efficacy (complete pathologic responses). RESULTS: From 7691 studies identified, 6370 were screened and 8 were included. Various agents, dosing regimens, and treatment durations were used, with durations of immunotherapy ranging from 1 to 16 cycles. Complete R0 resections were consistently achieved in 98% to 100% of resections. Of patients who received neoadjuvant immunotherapy and underwent resection, 50% to 91% had ypT0N0 pathology. The safety profiles were generally favorable, with grade 1 to 2 treatment-related adverse events (mostly immune-related) during immunotherapy reported in 22.2% to 70% of patients. Postoperative complications after neoadjuvant immunotherapy were reassuring, with no severe complications reported. LIMITATIONS: Small number of heterogeneous and uncontrolled studies precluding a meta-analysis. CONCLUSIONS: Neoadjuvant immune checkpoint inhibition is associated with high rates of pathologic complete responses in locally advanced colon cancer. The literature is limited, particularly for postoperative outcomes, and more studies are needed to understand the safety and positioning of these regimens in the neoadjuvant context.


Asunto(s)
Neoplasias del Colon , Reparación de la Incompatibilidad de ADN , Inmunoterapia , Terapia Neoadyuvante , Humanos , Terapia Neoadyuvante/métodos , Neoplasias del Colon/terapia , Neoplasias del Colon/genética , Neoplasias del Colon/inmunología , Neoplasias del Colon/patología , Inmunoterapia/métodos , Reparación de la Incompatibilidad de ADN/genética , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inestabilidad de Microsatélites
19.
Int Immunopharmacol ; 132: 111948, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38554445

RESUMEN

Cancer is attributed to uncontrolled cell growth and is among the leading causes of death with no known effective treatment while complex tumor microenvironment (TME) and multidrug resistance (MDR) are major challenges for developing an effective therapeutic strategy. Advancement in cancer immunotherapy has been limited by the over-activation of the host immune response that ultimately affects healthy tissues or organs and leads to a feeble response of the patient's immune system against tumor cells. Besides, traditional herbal medicines (THM) have been well-known for their essential role in the treatment of cancer and are considered relatively safe due to their compatibility with the human body. Yet, poor solubility, low bio-availability, and lack of understanding about their pathophysiological mechanism halt their clinical application. Moreover, considering the complex TME and drug resistance, the most precarious and least discussed concerns for developing THM-based nano-vaccination, are identification of specific biomarkers for drug inhibitory protein and targeted delivery of bioactive ingredients of THM on the specific sites in tumor cells. The concept of THM-based nano-vaccination indicates immunomodulation of TME by THM-based bioactive adjuvants, exerting immunomodulatory effects, via targeted inhibition of key proteins involved in the metastasis of cancer. However, this concept is at its nascent stage and very few preclinical studies provided the evidence to support clinical translation. Therefore, we attempted to capsulize previously reported studies highlighting the role of THM-based nano-medicine in reducing the risk of MDR and combating complex tumor environments to provide a reference for future study design by discussing the challenges and opportunities for developing an effective and safe therapeutic strategy against cancer.


Asunto(s)
Vacunas contra el Cáncer , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Inmunoterapia , Neoplasias , Microambiente Tumoral , Humanos , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunología , Animales , Inmunoterapia/métodos , Resistencia a Antineoplásicos/efectos de los fármacos , Vacunas contra el Cáncer/inmunología , Nanopartículas/química , Nanovacunas
20.
Value Health ; 27(6): 746-754, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38428815

RESUMEN

OBJECTIVES: This study aimed to determine the accuracy and consistency of established methods of extrapolating mean survival for immuno-oncology (IO) therapies, the extent of any systematic biases in estimating long-term clinical benefit, what influences the magnitude of any bias, and the potential implications for health technology assessment. METHODS: A targeted literature search was conducted to identify published long-term follow-up from clinical trials of immune-checkpoint inhibitors. Earlier published results were identified and Kaplan-Meier estimates for short- and long-term follow-up were digitized and converted to pseudo-individual patient data using an established algorithm. Six standard parametric, 5 flexible parametric, and 2 mixture-cure models (MCMs) were used to extrapolate long-term survival. Mean and restricted mean survival time (RMST) were estimated and compared between short- and long-term follow-up. RESULTS: Predicted RMST from extrapolation of early data underestimated observed RMST in long-term follow-up for 184 of 271 extrapolations. All models except the MCMs frequently underestimated observed RMST. Mean survival estimates increased with longer follow-up in 196 of 270 extrapolations. The increase exceeded 20% in 122 extrapolations. Log-logistic and log-normal models showed the smallest change with additional follow-up. MCM performance varied substantially with functional form. CONCLUSIONS: Standard and flexible parametric models frequently underestimate mean survival for IO treatments. Log-logistic and log-normal models may be the most pragmatic and parsimonious solutions for estimating IO mean survival from immature data. Flexible parametric models may be preferred when the data used in health technology assessment are more mature. MCMs fitted to immature data produce unreliable results and are not recommended.


Asunto(s)
Evaluación de la Tecnología Biomédica , Humanos , Neoplasias/mortalidad , Neoplasias/terapia , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inmunoterapia/métodos , Estimación de Kaplan-Meier , Análisis de Supervivencia , Sesgo , Factores de Tiempo
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