A Three-in-One Immunotherapy Nanoweapon via Cascade-Amplifying Cancer-Immunity Cycle against Tumor Metastasis, Relapse, and Postsurgical Regrowth

Li, Qian; Zhang, Di; Zhang, Jing; Jiang, Yue; Song, Aixin; Li, Zhonghao; Luan, Yuxia

doi:10.1021/acs.nanolett.9b02923

Cited by 105 publications

(78 citation statements)

References 38 publications

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“…As a result, the immune system remains inactive against malignant cells, allowing their uncontrolled growth and proliferation. The immune checkpoint inhibitors interfere with the action of these checkpoint proteins to prevent tumors from suppressing the T cells and restart the tumor immune cycle (Kieler et al, 2018;Li et al, 2019). Immune checkpoint inhibitors, in principle, should have a wide range of killing capabilities against cancer, but a large number of cases of non-response have been found in clinical applications (Ellmark et al, 2015; Coffelt and de Visser, 2016).…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

et al. 2020

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Bladder cancer is one of the most common malignant tumors of the urinary system that seriously threatens the health of a population. In recent years, the application of immunotherapy has significantly changed the treatment of bladder cancer, but only some patients can benefit from the treatment with immune-checkpoint inhibitors. Many problems are unsolved in the field of bladder cancer immunotherapy, especially in the search for genes that are critical to the level of immune cell infiltration and new effective therapeutic targets. We attempted to use bioinformatics analysis to identify immune gene markers related to the prognosis of bladder cancer and to establish a prognostic signature for bladder cancer patients based on their immune gene expression profiles. We used univariate Cox proportional hazards regression analysis, the least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox proportional hazards regression analysis from The Cancer Genome Atlas bladder cancer cohort (TCGA-BLCA). Fifteen genes related to prognosis were screened using the survival analysis, correlation analysis, cancer and adjacent cancer differential expression analysis, and mutation analysis. The potential biological role of these genes was determined using survival analysis and principal component analysis (PCA). The receiver operating characteristic (ROC) curve assesses the prognostic value of the predictive signature. The gene ontology (GO), Kyoto Encyclopedia of Gene and Genome (KEGG), Gene set enrichment analysis (GSEA), and other methods were used to reveal the differential gene enrichment in the signaling pathways and cellular processes of high-and low-risk groups. The single-sample GSEA (ssGSEA) method was used to quantify the infiltration levels of 24 immune cells in the tumor immune microenvironment and these immune genes were found to be closely related to the tumor immune microenvironment. In summary, we screened 15 immune genes that were closely related to bladder cancer overall survival (OS) and may be potential prognostic indicators of bladder cancer. They may have research and clinical application value in bladder cancer immunotherapy. We used 15 immune genes to construct a new immune-related gene signature that was verified and could be helpful in improving individualized prognosis of patients with bladder cancer.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

et al. 2020

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“…Li et al developed a three‐in‐one immunotherapy nanoplatform that can simultaneously promote TAA presentation, induce lymphocyte activation and proliferation, and inhibit tumor growth and metastasis ( Figure a). [ 69 ] This nanoplatform was synthesized by the self‐assembly of Ce6‐conjugated HC, 1MT‐conjugated polylysine (PM), and anti‐PD‐L1 monoclonal antibodies (aPD‐L1) (designated as aPD‐L1@HC/PM NPs). After accumulation at the tumor site, aPD‐L1@HC/PM NPs could effectively enter tumor cells and release aPD‐L1 to block the PD‐1/PD‐L1 signaling pathway via HAase‐activated charge reversal.…”

Section: Immunometabolic Therapy–based Multiple Therapymentioning

confidence: 99%

Recent Progress on Activatable Nanomedicines for Immunometabolic Combinational Cancer Therapy

Zhang

2020

Small Structures

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Cancer immunotherapy that stimulates the patient's immune system to eradicate cancer cells is a revolutionary strategy for the treatment of malignancies. [1] Compared to traditional chemotherapy and radiotherapy, which kill both cancer cells and normal cells, cancer immunotherapy can activate antitumor immune response to specifically target and eliminate cancer cells. [2] In general, the generation of antitumor immune response consists of a series of immunological processes. [3] First, tumor-associated antigens (TAAs) and danger-associated molecular patterns (DAMPs) are released from dying tumor cells. [4] Then, TAAs are captured by antigen-presenting cells (APCs), and DAMPs induce the activation and maturation of APCs. Activated APCs travel to lymph nodes and present TAAs on major histocompatibility complex I (MHC I) and MHC II molecules to T cells, leading to the activation of T cells. [5] Finally, activated T cells infiltrate the tumor tissues, recognize TAA-specific tumor cells, and release effector molecules (granzyme B and perforin) to kill tumor cells. [6] Up to now, several immunotherapies (e.g., immune checkpoint blockade (ICB), adoptive cell transfer, and cancer vaccine) that focus on the initiation and activation of antitumor immunity via various targets or mechanisms have been developed and achieved some progress in preclinical research and clinical translation. [7] Immunometabolic cancer therapy is an emerging therapeutic strategy that modulates tumor metabolic signaling pathways to activate immune cells to fight against tumors (Scheme 1a). [8] The proliferation and growth of cells generally involve a network of metabolic reactions (such as glycolysis, the tricarboxylic acid cycle, and amino acid metabolism). [9] In tumor cells, the dysregulation of cellular metabolic programs (e.g., nutrient limitation, immunosuppressive metabolites, and inhibitory immunometabolic signaling pathways) can lead to the failure of the immune system to fight against the tumor. [10] Tumor metabolic programs not only reflect the cellular state, but also play essential roles to restrict antigen presentation, initiate immune suppression or exhaustion, and impair the function of immune cells (including tumor-associated macrophages (TAMs), natural killer (NK) cells, effector T (T eff) cells, and regulatory T (T reg) cells). [11] Thereby, immunometabolic therapy that targets or modulates metabolic circuits to reprogram cancer metabolism can greatly attenuate tumor progression and reinvigorate antitumor immunity. [12] For example, inhibition of lactic acid production has been utilized to reduce tumor growth and unleash antitumor immunity; blockade of glutamine catabolism can inhibit the proliferation of tumor cells and recover the function and activity of TAMs and T eff cells. [8c] Thus, the development and advancement of immunometabolic therapies holds promise to improve the effectiveness of the treatment of cancer. Despite the progress, the clinical translation of cancer immunotherapies still faces some obstacles, such as immu...

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“…Second, the most immune checkpoint inhibitors were administered intravenously at a later stage, which act on immune cells universally rather than specific tumor antigens with the risks of inducing side effects (Shao et al, 2020 ). Linking UCNPs with immune checkpoint inhibitors together in a nanoplatform to release immune checkpoint inhibitors to tumor site through the enhanced permeability and retention (EPR) effect would be a promising strategy to improve the therapeutic efficacy of immunotherapy and reduce immune-related side effects (Li et al, 2019a ).…”

Section: Conclution and Outlookmentioning

confidence: 99%

Recent Advances on Rare Earth Upconversion Nanomaterials for Combined Tumor Near-Infrared Photoimmunotherapy

et al. 2020

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Cancer has been threatening the safety of human life. In order to treat cancer, many methods have been developed to treat tumor, such as traditional therapies like surgery, chemotherapy, radiotherapy, as well as new strategies like photodynamic therapy, photothermal therapy, sonodynamic therapy, and other emerging therapies. Although there are so many ways to treat tumors, these methods all face the dilemma that they are incapable to cope with metastasis and recurrence of tumors. The emergence of immunotherapy has given the hope to conquer the challenge. Immunotherapy is to use the body's own immune system to stimulate and maintain a systemic immune response to form immunological memory, resist the metastasis and recurrence of tumors. At the same time, immunotherapy can combine with other treatments to exhibit excellent antitumor effects. Upconversion nanoparticles (UCNPs) can convert near-infrared (NIR) light into ultraviolet and visible light, thus have good performance in bioimaging and NIR triggered phototherapy. In this review paper, we summarize the design, fabrication, and application of UCNPs-based NIR photoimmunotherapy for combined cancer treatment, as well as put forward the prospect of future development.

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A Three-in-One Immunotherapy Nanoweapon via Cascade-Amplifying Cancer-Immunity Cycle against Tumor Metastasis, Relapse, and Postsurgical Regrowth

Cited by 105 publications

References 38 publications

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

Bioinformatics Analysis Finds Immune Gene Markers Related to the Prognosis of Bladder Cancer

Recent Progress on Activatable Nanomedicines for Immunometabolic Combinational Cancer Therapy

Recent Advances on Rare Earth Upconversion Nanomaterials for Combined Tumor Near-Infrared Photoimmunotherapy

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