Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation

He, Teng; Hao, Zhixing; Lin, Mingjie; Xin, Zhongwei; Chen, Yongyuan; Ouyang, Wei; Yang, Qi; Chen, Xiaoke; Zhou, Hui; Zhang, Wanying; Wu, Pin; Xu, Feng

doi:10.1080/2162402x.2022.2093054

Cited by 19 publications

(13 citation statements)

References 64 publications

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“…[ 7 ] Previous studies have suggested that IT injection of STING agonists could normalize aberrant tumor vasculature and enhance anti‐tumor immunity. [ 22,39,40 ] However, systemic administration of these STING agonists has been limited because of their poor pharmacokinetic profiles and off‐target effects. [ 17 ] In this study, positively charged liposomes, PoSTING, enabled the systemic and tumor‐selective delivery of a STING agonist, remodeled tumor vasculature, and effectively elicited potent anti‐tumor immune responses.…”

Section: Discussionmentioning

confidence: 99%

Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis

Yang

Park

et al. 2023

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Although stimulator of interferon genes (STING) agonists has shown great promise in preclinical studies, the clinical development of STING agonist therapy is challenged by its limited systemic delivery. Here, positively charged fusogenic liposomes loaded with a STING agonist (PoSTING) are designed for systemic delivery and to preferentially target the tumor microenvironment. When PoSTING is administered intravenously, it selectively targets not only tumor cells but also immune and tumor endothelial cells (ECs). In particular, delivery of STING agonists to tumor ECs normalizes abnormal tumor vasculatures, induces intratumoral STING activation, and elicits robust anti‐tumor T cell immunity within the tumor microenvironment. Therefore, PoSTING can be used as a systemic delivery platform to overcome the limitations of using STING agonists in clinical trials.

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Section: Discussionmentioning

confidence: 99%

Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis

Yang

Park

et al. 2023

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“…19 IL-15 has been reported to activate STING pathway to promote TLS formation. He et al 221 demonstrated that oncolytic adenovirus encoding IL-15 (Ad-IL15) activated the STING-TBK1-IRF3 pathway in DCs, thereby promoting TLS formation and inhibiting tumor growth in a mouse model. In 2018, Hill et al 222 confirmed that the gp130/STAT3 pathway not only drives the occurrence of gastric adenocarcinoma, but also is directly related to the expression of CXCL13, CCL19, and CCL21, which initiate TLS genesis.…”

Section: Tls Induction By Molecular Driversmentioning

confidence: 99%

“…IL‐15 has been reported to activate STING pathway to promote TLS formation. He et al 221 . demonstrated that oncolytic adenovirus encoding IL‐15 (Ad‐IL15) activated the STING‐TBK1‐IRF3 pathway in DCs, thereby promoting TLS formation and inhibiting tumor growth in a mouse model.…”

Section: Clinical Implication Of Tls In Malignant Tumorsmentioning

confidence: 99%

Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications

Wang,

et al. 2024

MedComm

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Cancer is a major cause of death globally, and traditional treatments often have limited efficacy and adverse effects. Immunotherapy has shown promise in various malignancies but is less effective in tumors with low immunogenicity or immunosuppressive microenvironment, especially sarcomas. Tertiary lymphoid structures (TLSs) have been associated with a favorable response to immunotherapy and improved survival in cancer patients. However, the immunological mechanisms and clinical significance of TLS in malignant tumors are not fully understood. In this review, we elucidate the composition, neogenesis, and immune characteristics of TLS in tumors, as well as the inflammatory response in cancer development. An in‐depth discussion of the unique immune characteristics of TLSs in lung cancer, breast cancer, melanoma, and soft tissue sarcomas will be presented. Additionally, the therapeutic implications of TLS, including its role as a marker of therapeutic response and prognosis, and strategies to promote TLS formation and maturation will be explored. Overall, we aim to provide a comprehensive understanding of the role of TLS in the tumor immune microenvironment and suggest potential interventions for cancer treatment.

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“…The TLS dynamic influenced by heterogeneous anti-tumor therapies is one of the most recent controversial issues related to malignancies therapy. Recently, low-dose stimulator of interferon genes (STING) delivery to tumor microenvironment (TME) from various cancers induced vascular normalization and stimulated TLS neogenesis [ 19 , 20 , 21 ]. Tumor-associated TLSs were associated with a good prognosis for most types of cancer.…”

Section: Introductionmentioning

confidence: 99%

Tertiary Lymphoid Structures (TLSs) and Stromal Blood Vessels Have Significant and Heterogeneous Impact on Recurrence, Lymphovascular and Perineural Invasion amongst Breast Cancer Molecular Subtypes

Barb

Fenesan

Pirtea

et al. 2023

Cells

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Background: Tertiary lymphoid structures (TLSs) mediate local antitumor immunity, and interest in them significantly increased since cancer immunotherapy was implemented. We examined TLS− tumor stromal blood vessel interplay for each breast cancer (BC) molecular subtype related to recurrence, lymphovascular invasion (LVI), and perineural invasion (PnI). Methods: TLSs were quantified on hematoxylin and eosin stain specimens followed by CD34/smooth muscle actin (SMA) double immunostaining for stromal blood vessel maturation assessment. Statistical analysis linked microscopy to recurrence, LVI, and PnI. Results: TLS negative (TLS−) subgroups in each BC molecular subtype (except to Luminal A) have higher LVI, PnI, and recurrence. A significant rise in LVI and PnI were observed for the HER2+/TLS− subgroup (p < 0.001). The triple negative breast cancer (TNBC)/TLS− subgroup had the highest recurrence and invasion risk which was also significantly related to tumor grade. PnI but not LVI significantly influenced recurrence in the TNBC/TLS+ subgroup (p < 0.001). TLS−stromal blood vessel interrelation was different amongst BC molecular subtypes. Conclusion: BC invasion and recurrence are strongly influenced by TLS presence and stromal blood vessels, especially for HER2 and TNBC BC molecular subtypes.

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Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation

Cited by 19 publications

References 64 publications

Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis

Systemic Delivery of a STING Agonist‐Loaded Positively Charged Liposome Selectively Targets Tumor Immune Microenvironment and Suppresses Tumor Angiogenesis

Tertiary lymphoid structures in cancer: immune mechanisms and clinical implications

Tertiary Lymphoid Structures (TLSs) and Stromal Blood Vessels Have Significant and Heterogeneous Impact on Recurrence, Lymphovascular and Perineural Invasion amongst Breast Cancer Molecular Subtypes

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