Nanoparticles overcome adaptive immune resistance and enhance immunotherapy via targeting tumor microenvironment in lung cancer DOI Creative Commons
Xin Zhang, Xuemei Wang, Lijian Hou

et al.

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 24, 2023

Lung cancer is one of the common malignant cancers worldwide. Immune checkpoint inhibitor (ICI) therapy has improved survival lung patients. However, ICI leads to adaptive immune resistance and displays PD-1/PD-L1 blockade in cancer, leading less response Tumor microenvironment (TME) an integral tumor microenvironment, which involved immunotherapy resistance. Nanomedicine been used enhance cancer. In this review article, we described association between TME We also highlighted importance Moreover, discussed how nanoparticles are regulation improve efficacy immunotherapy, including SGT-53, AZD1080, Nanomodulator NRF2, Cisplatin nanoparticles, Au@PG, DPAICP@ME, SPIO NP@M-P, NBTXR3 ARAC Nano-DOX, MS NPs, Nab-paclitaxel, GNPs-hPD-L1 siRNA. Furthermore, concluded that targeting by could be helpful overcome

Language: Английский

Non-mutational neoantigens in disease DOI
Lawrence J. Stern, Cristina C. Clement, Lorenzo Galluzzi

et al.

Nature Immunology, Journal Year: 2024, Volume and Issue: 25(1), P. 29 - 40

Published: Jan. 1, 2024

Language: Английский

Citations

22
Copper-cysteamine nanoparticle-mediated microwave dynamic therapy improves cancer treatment with induction of ferroptosis DOI Creative Commons
Hui Zhou, Zhongtao Liu, Zijian Zhang

et al.

Bioactive Materials, Journal Year: 2022, Volume and Issue: 24, P. 322 - 330

Published: Dec. 28, 2022

Photodynamic Therapy (PDT) holds a great promise for cancer patients, however, due to the hypoxic characteristics of most solid tumors and limited penetration depth light in tissues, extensive clinical application PDT is limited. Herein, we report microwave induced copper-cysteamine (Cu-Cy) nanoparticles-based as promising treatment overcome resistance combination with ferroptosis. The efficiency Cu-Cy-mediated dynamic therapy (MWDT) tested on HCT15 colorectal (CRC) cells via cell titer-blue viability assay live/dead reveal that Cu-Cy upon MW irradiation can effectively destroy CRC average IC-50 values 20 μg/mL. cytotoxicity tumor after stimulation be alleviated by ferroptosis inhibitor. Furthermore, mediated MWDT could deplete glutathione peroxide 4 (GPX4) enhance lipid peroxides (LPO) malondialdehyde (MDA). Our findings demonstrate MW-activated killed inducing superior vivo antitumor efficacy was corroborated tumor-bearing mice model. Immunohistochemical experiments showed GPX4 expression level + group significantly lower than other groups. Overall, these nanoparticles have safe prospect deep-seated inhibit proliferation ferroptosis, which provides potential solution resistance.

Language: Английский

Citations

47
Exosomal cargos-mediated metabolic reprogramming in tumor microenvironment DOI Creative Commons

Shiming Tan,

Yiqing Yang, Wenjuan Yang

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2023, Volume and Issue: 42(1)

Published: March 10, 2023

Metabolic reprogramming is one of the hallmarks cancer. As nutrients are scarce in tumor microenvironment (TME), cells adopt multiple metabolic adaptations to meet their growth requirements. not only present cells, but exosomal cargos mediates intercellular communication between and non-tumor TME, inducing remodeling create an outpost microvascular enrichment immune escape. Here, we highlight composition characteristics meanwhile summarize components corresponding sorting mode. Functionally, these cargos-mediated improves "soil" for metastasis. Moreover, discuss abnormal metabolism targeted by its potential antitumor therapy. In conclusion, this review updates current role TME enriches future application scenarios exosomes.

Language: Английский

Citations

39
Dendritic Nanomedicine with Boronate Bonds for Augmented Chemo‐Immunotherapy via Synergistic Modulation of Tumor Immune Microenvironment DOI Open Access
Yunkun Li, Yahui Wu,

Zaixiang Fang

et al.

Advanced Materials, Journal Year: 2023, Volume and Issue: 36(2)

Published: Sept. 25, 2023

Unsatisfied tumor accumulation of chemotherapeutic drugs and a complicated immunosuppressive microenvironment diminish the immune response rate therapeutic effect. Surface modification these with target ligands can promote their cellular internalization, but modified may be subjected to unexpected recognition clearance. Herein, phenylboronic acid (PBA) group-shieldable dendritic nanomedicine that integrates an immunogenic cell death (ICD)-inducing agent (epirubicin, Epi) indoleamine 2,3-dioxgenase 1 (IDO1) inhibitor (NLG919) is reported for chemo-immunotherapy. This NLG919-loaded Epi-conjugated PEGylated dendrimers bridged boronate bonds (NLG919@Epi-DBP) maintains stable nanostructure during circulation. Under moderate acidic condition, PBA group exposes sialic residue on membrane enhance internalization penetration NLG919@Epi-DBP. At pH 5.0, NLG919@Epi-DBP rapidly disassembles release incorporated Epi NLG919. triggers robust ICD cells evokes strong response. In addition, inhibition IDO1 activity downregulates metabolism L-tryptophan kynurenine, leading reduction in recruitment modulation microenvironment. Collectively, this promising strategy has been demonstrated evoke as well remodel enhanced chemo-immunotherapeutic

Language: Английский

Citations

37
Bispecific antibodies targeting immunomodulatory checkpoints for cancer therapy DOI Creative Commons
Tiancheng Zhang, Youpei Lin, Qiang Gao

et al.

Cancer Biology and Medicine, Journal Year: 2023, Volume and Issue: 20(3), P. 181 - 195

Published: March 24, 2023

Advances in antibody engineering have led to the generation of more innovative drugs, such as bispecific antibodies (bsAbs). Following success associated with blinatumomab, bsAbs attracted enormous interest field cancer immunotherapy. By specifically targeting two different antigens, reduce distance between tumor and immune cells, thereby enhancing killing directly. There are several mechanisms action upon which been exploited. Accumulating experience on checkpoint-based therapy has promoted clinical transformation immunomodulatory checkpoints. Cadonilimab (PD-1 × CTLA-4) is first approved bsAb dual inhibitory checkpoints, confirms feasibility In this review we analyzed by checkpoints their emerging applications

Language: Английский

Citations

34
Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma DOI Creative Commons

Yu‐Ting Xue,

Xuejiao Jiang,

Junrong Wang

et al.

Biomarker Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: Jan. 5, 2023

Abstract Head and neck cancer is a malignant tumour with high mortality rate characterized by late diagnosis, recurrence metastasis rates, poor prognosis. squamous cell carcinoma (HNSCC) the most common type of head cancer. Various factors are involved in occurrence development HNSCC, including external inflammatory stimuli oncogenic viral infections. In recent years, studies on regulation death have provided new insights into biology therapeutic response such as apoptosis, necroptosis, pyroptosis, autophagy, ferroptosis, recently newly discovered cuproptosis. We explored how various deaths act unique defence mechanism against emergence they can be exploited to inhibit tumorigenesis progression, thus introducing regulatory (RCD) novel strategy for therapy. contrast accidental death, RCD controlled specific signal transduction pathways, TP53 signalling, KRAS NOTCH hypoxia metabolic reprogramming. this review, we describe molecular mechanisms nonapoptotic its relationship HNSCC discuss crosstalk between relevant signalling pathways cells. also highlight approaches elimination through RCD.

Language: Английский

Citations

28
The E3 ubiquitin ligases regulate PD-1/PD-L1 protein levels in tumor microenvironment to improve immunotherapy DOI Creative Commons
Bo Hou, Ting Chen, He Zhang

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Jan. 17, 2023

The tumor microenvironment (TME) is the surrounding environment, which critical for development and progression. TME also involved in clinical intervention treatment outcomes. Modulation of useful improving therapy strategies. PD-L1 protein on cells interacts with PD-1 T cells, contributing to cell dysfunction exhaustion, blockage immune response. Evidence has demonstrated that expression PD-1/PD-L1 associated response anti-PD-1/PD-L1 cancer patients. It important discuss regulatory machinery how finely regulated cells. In recent years, studies have was governed by various E3 ubiquitin ligases TME, resistance human cancers. this review, we will role molecular mechanisms ligases-mediated regulation TME. Moreover, describe ligases-involved alters efficacy. Altogether, targeting control levels could be a potential strategy potentiate immunotherapeutic effects

Language: Английский

Citations

26
Inhibition of CDC20 potentiates anti-tumor immunity through facilitating GSDME-mediated pyroptosis in prostate cancer DOI Creative Commons
Fei Wu,

Minglei Wang,

Tao Zhong

et al.

Experimental Hematology and Oncology, Journal Year: 2023, Volume and Issue: 12(1)

Published: Aug. 1, 2023

Abstract Background Increasing evidence suggests that immunotherapy, especially immune checkpoint inhibitors (ICIs), has the potential to facilitate long-term survival in various cancer besides prostate cancer. Emerging indicated pyroptosis, an immunogenic form of cell death, could trigger anti-tumor microenvironment and enhance effectiveness immunotherapy. Nevertheless, mechanism underlying regulation pyroptosis signaling remains unclear. Methods The differential expression human E3 ligases was integratedly analyzed from five independent public datasets. Moreover, immunohistochemistry analysis a tissue microarray derived patients confirmed results bioinformatic analysis. Furthermore, lines were evaluated via next-generation RNA sequencing assess transcriptomic profile upon CDC20 depletion. Next, qRT-PCR, Western blotting, cycloheximide assay, immunoprecipitation, ubiquitination assay employed explore correlation interaction between GSDME. Both immune-deficient immune-competent murine models utilized examine efficacy inhibition with or without anti-PD1 antibodies, respectively. To analyze xenografts, tumor tissues examined by flow cytometry. Results multiple cohorts suggested most significantly over-expressed ligase. In addition, exerted negative regulatory effect on pathway targeting GSDME for ubiquitination-mediated proteolysis degron-dependent manner. Knockdown leads increased abundance transition apoptosis response death signals. our syngeneic models, we found depletion enhances immunity promoting infiltration CD8 + T lymphocytes dependent existence GSDME, as well reducing myeloid cells. More importantly, Apcin, small molecular inhibitor targets CDC20, exhibited synergistic effects anti-PD1-based immunotherapy Conclusions Overall, these findings provide new insights into upstream GSDME-mediated which specifically interacts facilitates its Importantly, data highlight novel pathways cellular enhancing

Language: Английский

Citations

23
Exploiting Tertiary Lymphoid Structures to Stimulate Antitumor Immunity and Improve Immunotherapy Efficacy DOI Creative Commons
Giulia Petroni, Serena Pillozzi, Lorenzo Antonuzzo

et al.

Cancer Research, Journal Year: 2024, Volume and Issue: 84(8), P. 1199 - 1209

Published: Feb. 21, 2024

Abstract Tumor-associated tertiary lymphoid structures (TLS) have been associated with favorable clinical outcomes and response to immune checkpoint inhibitors in many cancer types, including non–small cell lung cancer. Although the detailed cellular molecular mechanisms underlying these associations not fully elucidated, growing preclinical studies are helping elucidate at basis of TLS formation, composition, regulation responses. However, a major challenge remains how exploit enhance naïve treatment-mediated antitumor Here, we discuss current understanding tumor-associated TLS, models that can be used study them, potential therapeutic interventions boost particular focus on research.

Language: Английский

Citations

12
Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment DOI Creative Commons
Fusheng Zhang,

Junchen Guo,

Shengmiao Yu

et al.

Cancer Communications, Journal Year: 2024, Volume and Issue: 44(9), P. 929 - 966

Published: July 12, 2024

Abstract The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features TME include metabolic reprogramming, hypoxia, chronic inflammation, immunosuppression. Previous studies suggest that senescence‐associated secretory phenotypes mediate intercellular information exchange play a role in dynamic evolution TME. Specifically, hypoxic adaptation, dysregulation, phenotypic shifts immune cells regulated by cellular senescence synergistically contribute to development an immunosuppressive thereby promoting progression events. This review provides comprehensive summary processes which regulates tumor‐adapted TME, with focus on complex underlying relationship between changes biological functions cells. available findings components collectively potential applications challenges targeted senescence‐based combination therapies clinical settings are further discussed within context advancing senescence‐related research.

Language: Английский

Citations

12