Combination of an autophagy inhibitor with immunoadjuvants and an anti-PD-L1 antibody in multifunctional nanoparticles for enhanced breast cancer immunotherapy

Cheng, Yang; Wang, Caixia; Zhang, Zhiwei; Yang, Xiaopeng; Dong, Yanming; Ma, Li; Luo, Jingwen

doi:10.1186/s12916-022-02614-8

Cited by 29 publications

(22 citation statements)

References 56 publications

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“…GIMAP6 was closely related to the occurrence of autophagy. Autophagy was a double-edged sword in the immune microenvironment: it can inhibit or promote the occurrence and development of tumors by regulating the immune response [29][30][31] . Autophagy regulated T cell differentiation and survival, and regulatory T cells with autophagy defects promoted apoptosis and function defects of itself, leading to tumor resistance 32,33 .…”

Section: Discussionmentioning

confidence: 99%

Investigation and verification of GAMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma

Chen

Zhou

et al. 2023

Preprint

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Background and aim: It has been reported GIMAP6 was crucial for autophagy. But it is unknown the role of GIMAP6 in occurrence and tumor-immunity of lung adenocarcinoma. Methods: Comprehensive analyses for datasets from TCGA and GTEx databases were conducted by R software. Basic experiments including RT-qPCR, CCK-8 assays, colony formation assay and transwell assays were applied to explore the role of GIMAP6 in vivo and vitro. Prognostic features and GIMAP6 were applied to construct nomogram. Potential mechanism of GIMAP6 in lung adenocarcinoma was investigated by GO, KEGG and GESA. The correlation between GIMAP6 and immune landscape has also been explored using scRNA sequencing datasets from Timer 2.0 and TISCH. Results: The OS and DSS of lung adenocarcinoma patients with high GIMAP6 expression was better than that with low GIMAP6 expression. The nomogram based on T stage, N stage, and GIMAP6 had predictive significance for prognosis, which was identified by ROC and calibration curve. Functional enrichment analysis suggested that GIMAP6 was mainly involved in T-cell receptor signaling pathway, chemokine signaling pathway, cytokine and cytokine receptor interaction. Single cell sequencing and TIMER2.0 analysis illustrated that GIMAP6 was positively correlated with the infiltration of immune cells and immune-relate molecules including CTLA4, PD-L1, and TIGIT. Basic experiments confirmed the role of GIMAP6 in the proliferation, invasion and migration of lung adenocarcinoma cells. Conclusion: We confirmed that GIMAP6 was an effective prognostic molecule and involved in the regulation of the immune microenvironment of lung adenocarcinoma, which may become a predictor for the efficacy of immunotherapy.

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Section: Discussionmentioning

confidence: 99%

Investigation and verification of GAMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma

Chen

Zhou

et al. 2023

Preprint

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“…We have previously shown that treatment with anti-PD-1 antibody was effective at prolonging survival in murine LAM (17). In addition, CpG has been shown to enhance anti-tumor immunity in pre-clinical cancer models when given in combination with chemotherapy or checkpoint inhibition (32)(33)(34). Therefore, we conducted a survival study to evaluate combination therapy of CpG with checkpoint inhibition to determine potential synergistic effects in LAM treatment.…”

Section: Combination Cpg and Anti-pd1 Therapy Work Synergistically To...mentioning

confidence: 99%

Plasmacytoid dendritic cells mediate CpG-ODN induced increase in survival in a mouse model of lymphangioleiomyomatosis

Amosu

McCright

Yang

et al. 2023

Preprint

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Rationale: Lymphangioleiomyomatosis (LAM) is a devastating disease primarily found in women of reproductive age that leads to cancer-like cystic destruction of the lungs. Recent work has shown that LAM causes immunosuppression and that checkpoint inhibitors can be used as LAM treatment. IN lung cancer, TLR agonist, in particular TLR9 agonist CpG has been shown to be effective. Objectives: Here we investigate the use of TLR9 agonist CpG as LAM immunotherapy in combination with checkpoint inhibitor, anti-PD1 and assess induced changes in anti-LAM immunity. Methods: We used a murine model of metastatic LAM to determine survival after intranasal treatment with TLR9 agonist CpG at two doses and in combination the checkpoint inhibitor immunotherapy, anti-PD-1. We used histology and flow cytometry to assess overall inflammation as well as changes in the immune response upon treatment. Measurements and Main Results: We found that local administration of CpG enhances survival in a murine model of LAM and that a lower dose more effectively balanced the inflammation induced by CpG with the anti-LAM therapeutic benefits. We also found that CpG reduces regulatory T cell infiltration in LAM lungs and that CD4 helper T cells are skewed toward pro-inflammatory phenotypes. We also found that CpG treatment is effective in both early stage and progressive disease and that CpG is synergistic with previously tested anti-PD1 therapy. Conclusions: We have found that TLR9 agonist CpG can be used as LAM immunotherapy and effectively synergizes with anti-PD1 therapy in LAM.

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“…Breast cancer is one of the three most common cancers and the most commonly occurring cancer in women, and it presents the leading cause of death in women throughout the world [1]. Anti-cancer therapy for breast tumors is challenging due to the highly metastatic progression of the disease to other organs, such as lung, liver, and bone [2,3]. Chemoimmunotherapy is very promising for its applications in metastatic breast cancer therapy [4].…”

Section: Commentarymentioning

confidence: 99%

“…Recently, Cheng et al [2] first constructed a PD-L1-and CD44-responsive multilayered nanoplatform through a convenient, ultrafast and universal self-assembly route. The developed MNPs were loaded with two chemotherapeutic drugs (paclitaxel (PTX) and Chloroquine (CQ)) in the core, an immunopotentiator (CpG) and an antigen (ovalbumin (OVA)) in the middle, and an immune checkpoint inhibitor (anti-PD-L1 antibody, also known as atezolizumab) at the outer layer (Figure 1A).…”

Section: Commentarymentioning

confidence: 99%

Towards a Chemo-immunotherapy to Improve Breast Cancer Immunotherapy

2023

Journal of Cellular Immunology

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Chemo-immunotherapy has shown great promise as a next-generation treatment strategy for established solid tumors. Cheng et al. first developed the PD-L1-and CD44-responsive multifunctional nanoparticles (MNPs) utilizing a polymer complex of polyethyleneimine and oleic acid (PEI-OA) and loaded with two chemotherapeutic drugs (paclitaxel and chloroquine), an antigen (ovalbumin), an immunopotentiator (CpG), and an immune checkpoint inhibitor (anti-PD-L1 antibody). PEI-OA increases the drug loading capacity and encapsulation efficiency of the nanoplatform. Anti-PD-L1 antibody promotes its cellular uptake, increases the levels of CD4 + and CD8 + T cells and inhibits primary breast cancer at the tumor site. Paclitaxel triggers tumor cells apoptosis directly, and then produces tumor vaccines to promote the dendritic cells (DCs) maturation, finally primes the T cells activation. Ovalbumin as a model antigen and CpG as an immunopotentiator to stimulate the DCs maturation. Moreover, chloroquine turns the "immune-cold" environment and potentiates the anti-tumor effect of both immune checkpoint inhibitor and chemotherapeutics, thus synergically and efficiently improving the breast cancer immunotherapy.

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Combination of an autophagy inhibitor with immunoadjuvants and an anti-PD-L1 antibody in multifunctional nanoparticles for enhanced breast cancer immunotherapy

Cited by 29 publications

References 56 publications

Investigation and verification of GAMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma

Investigation and verification of GAMAP6 as a robust biomarker for prognosis and tumor immunity in lung adenocarcinoma

Plasmacytoid dendritic cells mediate CpG-ODN induced increase in survival in a mouse model of lymphangioleiomyomatosis

Towards a Chemo-immunotherapy to Improve Breast Cancer Immunotherapy

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