An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma

Lasso, Paola; Gomez-Cadena, Alejandra; Urueña, Claudia; Donda, Alena; Martinez‐Usatorre, Amaia; Romero, Pedro; Barreto, Alfonso; Fiorentino, Susana

doi:10.3389/fimmu.2020.584959

Cited by 26 publications

(13 citation statements)

References 60 publications

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“…The t-SNE analysis of tumor tissues from mice after different treatments indicated a decrease in MDSC-LC and an increase in DCs in animals treated with both extracts, compared with the PBS group ( Figure 4 C). Add to this, mice treated with P2Et and T. usneoides had an increased frequency of activated CD8 + CD44 + T cells ( Figure 4 D), suggesting that T. usneoides extract, as well as P2Et, as previously shown [ 27 , 28 ], may enhance the antigenic presentation and limit the infiltration of MDSC-LC in the TME. In the B16-F10 model, we only observed the increase in tumor-infiltrating immune cells in mice treated with P2Et, but not with T. usneoides ( Figure 4 E).…”

Section: Resultssupporting

confidence: 71%

“…In order to evaluate whether the differences observed at the cellular level were manifested in a different sensitivity of each tumor to in vivo treatment, we evaluated the effect of the T. usneoides extract on the control of tumor growth ( Figure 3 A). Cells of 4T1 or B16-F10 were transplanted to BALB/c and C57BL/6 mice respectively and when tumors were established after 5 days, mice were treated with 142.5 mg/Kg body weight of T. usneoides extract previously calculated in an acute toxicity test (described in Section 2 ), P2Et extract (positive control) [ 27 , 28 ], or PBS (negative control). In the 4T1 breast cancer model, animals treated with T. usneoides displayed a significant delay in tumor progression, even greater than our positive control P2Et ( Figure 3 B; Supplementary Materials, Figure S3A ).…”

Section: Resultsmentioning

confidence: 99%

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Tillandsia usneoides Extract Decreases the Primary Tumor in a Murine Breast Cancer Model but Not in Melanoma

Lasso

Rojas

Arévalo

et al. 2022

Cancers

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The main limits of current antitumor therapies are chemoresistance, relapses, and toxicity that impair patient quality of life. Therefore, the discovery of therapeutic alternatives, such as adjuvants to conventional therapy that modulate the intracellular oxidation state or the immune response, remains a challenge. Owing to traditional medicine, several uses of plants are known, indicating a promising antitumor and immunomodulatory effect. We evaluated the effect of ethanolic extract of T. usneoides in vitro and in vivo in models of 4T1 breast cancer and B16-F10 melanoma. In vitro evaluations with both cell lines showed that the extract has cytotoxic activity and induces apoptotic cell death. However, its effect on ROS production and glucose uptake was opposite. In vivo, only in the 4T1 model, a significant decrease in tumor size was found in animals treated with the extract, accompanied by an increase in dendritic cells and activated CD8+ T cells, and a decrease in myeloid-derived suppressor-like cells (MDSC-LC) and Tregs in the tumor microenvironment. These results suggest that T. usneoides extract antagonistically regulates tumor metabolism of 4T1 vs. B16-F10, impacting the tumor microenvironment and effective antitumor immune response, leading to a reduction in 4T1 tumor size but not on B16-F10.

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Section: Resultssupporting

confidence: 71%

Section: Resultsmentioning

confidence: 99%

Tillandsia usneoides Extract Decreases the Primary Tumor in a Murine Breast Cancer Model but Not in Melanoma

Lasso

Rojas

Arévalo

et al. 2022

Cancers

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“…Notably, TNBC presenting high TILs may have upregulated PD-L1 expression [ 32 ], and conversely, its decrease induced by OTUB1 ablation can reduce its protein binding to the tumor cell surface, facilitate more CD8 T cell infiltration and increase the serum level of interferon-γ to enhance anti-tumor immunity in mice [ 33 ]. More importantly, PD-L1 shows an anti-tumor effect with no clear additive effects in 4T1 tumor-bearing mouse models of breast cancer [ 34 ]. Photothermal therapy has been reported to enhance cancer immunotherapy since it has immune-stimulation functions and subsequently triggers anti-tumor immune responses [ 35 ], this is very much consistent with our results, suggesting the promising usage of IM@ZP as a photothermal agent to treat TNBC.…”

Section: Discussionmentioning

confidence: 99%

IR792-MCN@ZIF-8-PD-L1 siRNA drug delivery system enhances photothermal immunotherapy for triple-negative breast cancer under near-infrared laser irradiation

Wang

Song

et al. 2022

J Nanobiotechnol

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Background Despite extensive investigations on photothermal therapy, the clinical application is restricted due to poor stability, low therapeutic efficacy of photothermal therapy agents and its affinity loss in the multistep synthesis of delivery carriers. To address this, we designed an IR792-MCN@ZIF-8-PD-L1 siRNA (IM@ZP) nanoparticle drug delivery system. IM@ZP was prepared by in situ synthesis and physical adsorption, followed by characterization. Photothermal conversion ability of IM@ZP was assessed by irradiation of near-infrared (NIR) laser, followed by analysis of its effect on 4T1 cell viability, maturation of dendritic cells (DCs) and the secretion of related cytokines in vitro, and the changes of tumor infiltrating T cells and natural killer (NK) cells in vivo. Subcutaneous 4T1 tumor-bearing mouse and lung metastasis models were established to investigate the role of IM@ZP in killing tumor and inhibiting metastasis in vivo. Results IM@ZP was uniform nanoparticles of 81.67 nm with the characteristic UV absorption peak of IR792, and could effectively adsorb PD-L1 siRNA. Under the irradiation of 808 nm laser, IM@ZP exhibited excellent photothermal performance. IM@ZP could be efficiently uptaken by 4T1 cells, and had high transfection efficiency of PD-L1 siRNA. Upon NIR laser irradiation, IM@ZP effectively killed 4T1 cells, upregulated HSP70 expression, induced DC maturation and increased secretion of TNF-α and IL-6 in vitro. Moreover, in vivo experimental results revealed that IM@ZP enhanced photothermal immunotherapy as shown by promoted tumor infiltrating CD8 + and CD4 + T cells and NK cells, and inhibited tumor growth and lung metastasis. Conclusion Together, biocompatible IM@ZP nanoparticles result in high photothermal immunotherapy efficiency and may have a great potential as a delivery system for sustained cancer therapy. Graphical Abstract

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“…The existing polyphenol nano-drug delivery technology may have great potential in this regard [ 121 ]. In fact, studies have demonstrated that polyphenols can provide a powerful environment for tumor immunotherapy by regulating the tumor immune microenvironment (TME) [ 122 ]. Conversely, there are indications that polyphenols may also play harmful roles [ 123 ], which means we should choose carefully when immunotherapy is used [ 124 ].…”

Section: Summary and Challengementioning

confidence: 99%

Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review

Zheng

Zhao

et al. 2022

Current Oncology

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The lack of new drugs and resistance to existing drugs are serious problems in gastric cancer(GC) treatment. The research found polyphenols possess anti-Helicobacter pylori(Hp) and antitumor activities and may be used in the research and development of drugs for cancer prevention and treatment. However, polyphenols are affected by their chemical structures and physical properties, which leads to relatively low bioavailability and bioactivity in vivo. The intestinal flora can improve the absorption, utilization, and biological activity of polyphenols, whereas polyphenol compounds can increase the richness of the intestinal flora, reduce the activity of carcinogenic bacteria, stabilize the proportion of core flora, and maintain homeostasis of the intestinal microenvironment. Our review summarizes the gastrointestinal flora-mediated mechanisms of polyphenol against GC.

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An Immunomodulatory Gallotanin-Rich Fraction From Caesalpinia spinosa Enhances the Therapeutic Effect of Anti-PD-L1 in Melanoma

Cited by 26 publications

References 60 publications

Tillandsia usneoides Extract Decreases the Primary Tumor in a Murine Breast Cancer Model but Not in Melanoma

Tillandsia usneoides Extract Decreases the Primary Tumor in a Murine Breast Cancer Model but Not in Melanoma

IR792-MCN@ZIF-8-PD-L1 siRNA drug delivery system enhances photothermal immunotherapy for triple-negative breast cancer under near-infrared laser irradiation

Polyphenol Mechanisms against Gastric Cancer and Their Interactions with Gut Microbiota: A Review

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