The application of immune checkpoint blockade in breast cancer and the emerging role of nanoparticle

Masoumi, Elham; Tahaghoghi-Hajghorbani, Sahar; Jafarzadeh, Leila; Sanaei, Mohammad‐Javad; Pourbagheri‐Sigaroodi, Atieh; Bashash, Davood

doi:10.1016/j.jconrel.2021.10.018

Cited by 28 publications

(21 citation statements)

References 218 publications

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“…Immunotherapy is becoming the most promising strategy for cancer treatment, and immune checkpoint blockade is major part of immunotherapy. [ 55 ] We also revealed that NT5DC family members were strongly associated with immune checkpoints and played vital roles in tumor immune microenvironment. Therefore, the combination of immunotherapy and chemotherapy targeting NT5DC family could provide a novel therapeutic option for breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of NT5DC family prognostic and immune significance in breast cancer

Jia

et al. 2023

Medicine

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Among the most common malignancies, breast cancer has a high incidence and mortality rate. NT5DC family is a highly well-conserved 5′-nucleotidase. Previous studies showed that the progression of tumors was associated with some NT5DC family members. However, there are no studies about the comprehensive analysis such as expression, prognosis, and immune properties of NT5DC family in breast cancer. Based on the data from The Cancer Genome Atlas database, we used UALCAN, Tumor Immune Estimation Resource, Breast cancer gene-expression miner (Bc-GenExMiner), Kaplan–Meier Plotter, TISIDB, cBioPortal, GeneMANIA, Search Tool for the Retrieval of Interacting Genes, Metascape, Tumor Immune Single-cell Hub, The Database for Annotation, Visualization and Integrated Discovery, and Gene Set Cancer Analysis databases to explore expression, prognostic and diagnostic value, genetic alterations, biological function, immune value and drug sensitivity of NT5DC family in breast cancer patients. There was a downregulation of NT5C2, NT5DC1, and NT5DC3 in breast cancer compared to normal tissues, and NT5DC2 instead. All NT5DC family members were associated with the clinicopathological parameters of breast cancer patients. Survival and ROC analysis revealed that NT5DC family genes were related to the prognosis and diagnosis of breast cancer. NT5DC family were mainly involved in nucleotide metabolism. Moreover, NT5DC family were significantly associated with tumor immune microenvironment, diverse immune cells, and immune checkpoints in breast cancer. This research showed that NT5DC family might be novel prognostic biomarkers and immunotherapeutic targets of breast cancer.

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Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of NT5DC family prognostic and immune significance in breast cancer

Jia

et al. 2023

Medicine

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“…31,32 Recent advances in nanoparticle-based immune check point inhibitor therapy have improved the anti-tumor immunity against various types of malignancies, including NSCLC. [33][34][35] Our findings reveal that Tregs immunosuppressive signaling can be restrained in both in vivo and ex vivo by using a CuS/EPDA photothermal nanocarrier model. The combinational use of epacadostat, an inhibitor of immunosuppression and IDO-1 and Dasatinib, a multikinase inhibitor that prevents the proliferation and function of CD4 + CD25 + regulatory cells, shows promising results.…”

Section: Discussionmentioning

confidence: 75%

Engineered Hybrid Treg-Targeted Nanosomes Restrain Lung Immunosuppression by Inducing Intratumoral CD8+T Cell Immunity

Domvri¹,

Petanidis²,

Anestakis³

et al. 2022

IJN

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Introduction Tumor immunotherapy is a key therapeutic paradigm for the treatment of several malignancies. However, in metastatic lung cancer, classical immunotherapy regimes are ineffective due to regulatory T cell (Treg)-related immunosuppression and tumor relapse. Materials To address this issue, we designed specific biocompatible Treg-targeted nanocarriers (NCs) as a model of immune-based nanotherapy, in order to target Treg-related immunosuppression in the lung tumor microenvironment. This is achieved through the combination of Dasatinib and Epacadostat integrated into biodegradable nanosomes which can inhibit and reverse Treg-supporting immunosuppression. Flow cytometry and immunofluorescence analysis, PET/CT scan, PTT/PA imaging and the Balb/c tumor model were used to explore the anti-tumor effect of Treg-targeted NCs both in vitro and in vivo. Results Findings reveal that NC treatment triggered substantial tumor cell apoptosis and drastically decreased tumor volume followed by downregulation of Ki-67 antigen expression, respectively. Drug circulation time was also increased as shown by biodistribution analysis accompanied by greater accumulation in lung and peripheral tissues. Intratumoral Th1 cytokines’ expression was also increased, especially TNF-A, IL-12 by 42%, and IL-6 by 18% compared to PBS treatment. In addition, the presence of mature CD80 + /CD86 + dendritic cells (DCs) revealed T cell enrichment and a decline in MDSC infiltration and myeloid subsets. Interestingly, a significant decline of Gr/CD11b myeloid cell population in blood and tissue samples was also observed. This immune activation can be attributed to the enhanced PTT efficiency and tumor targeting ability of the nanospheres which under near infrared (NIR) exposure can prompt highly efficient tumor ablation. We also demonstrated their therapeutic efficacy against 4T1 metastatic breast cancer model. Additionally, the photothermal therapy in combination with PD-L1 checkpoint blockade therapy exerted long-term tumor control over both primary and distant tumors. Discussion Overall, our findings present a novel nano-enabled platform for the inhibition of Treg-dependent immunosuppression in NSCLC and provide a novel nanotherapeutic strategy for the treatment of metastatic neoplasia.

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“…Similarly, the loss or inactivation of some tumor suppressor genes, such as TP53, PTEN, Rb and CDNK2A, is a common molecular event [ 26 ]. There is also the expression and interaction of immune checkpoint molecules between tumor cells and immune cells to protect cancer cells from the attack of immune cells, such as PD-1, PD-L1, CTLA-4, LAG-3, ID-1 and tim-3 [ 5 , 27 ]. Changes in the function of these genes lead to activation or inactivation in a series of downstream signaling pathways and remodeling of the TME.…”

Section: Discussionmentioning

confidence: 99%

Chimeric Oncolytic Adenovirus Armed Chemokine Rantes for Treatment of Breast Cancer

et al. 2022

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The immunosuppressive state in the tumor microenvironment (TME) of breast cancer makes it difficult to treat with immunotherapy. Oncolytic viruses not only lyse tumor cells but also reshape the TME. Therefore, they can play a multi-mechanism synergistic effect with immunotherapy. In this study, an oncolytic adenovirus Ad5F11bSP-Rantes was constructed and used as a vector to express the chemokine Rantes. The objective of this study was to test the dual mechanisms of the oncolytic effect mediated by virus replication and the enhanced anticancer immune response mediated by Rantes chemotaxis of immune cells. It was found that Ad5F11bSP-Rantes has strong infectivity and effective killing activity against breast cancer cells. In the established triple negative breast cancer (TNBC) xenograft model in NCG mice whose immune system was humanized with human peripheral blood mononuclear cells (PBMCs), Ad5F11bSP-Rantes achieved 88.33% tumor inhibition rate. Rantes expression was high in mouse blood, a large number of CD3+ lymphocytes infiltrated in tumor tissues and E-cadherin was up-regulated in cancer cells, suggesting that Ad5F11bSP-Rantes altered the TME and induced a reversal of cancer cell epithelial–mesenchymal transition (EMT). In conclusion, oncolytic adenovirus can exert the oncolytic effect and the chemotactic effect of immune cells and realize the synergy of multiple anticancer effects. This strategy creates a candidate treatment for the optimization of breast cancer, especially TNBC, combination therapy.

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The application of immune checkpoint blockade in breast cancer and the emerging role of nanoparticle

Cited by 28 publications

References 218 publications

Comprehensive analysis of NT5DC family prognostic and immune significance in breast cancer

Comprehensive analysis of NT5DC family prognostic and immune significance in breast cancer

Engineered Hybrid Treg-Targeted Nanosomes Restrain Lung Immunosuppression by Inducing Intratumoral CD8+T Cell Immunity

Chimeric Oncolytic Adenovirus Armed Chemokine Rantes for Treatment of Breast Cancer

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