The Role of Anti-angiogenesis in the Treatment Landscape of Non-small Cell Lung Cancer – New Combinational Approaches and Strategies of Neovessel Inhibition

Daum, Sophia; Hagen, Hannes; Naismith, Erin; Wolf, Dominik; Pircher, Andreas

doi:10.3389/fcell.2020.610903

Cited by 34 publications

(39 citation statements)

References 143 publications

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“…HEVs in TLSs are associated with T and B cell infiltration and indicate favorable outcomes in oral carcinoma and breast cancer ( 72 , 73 ). The emergence of HEVs also contributes to the formation of TLSs ( 74 ). There is ample evidence that the function of HEVs in TLSs is similar to that in LNs, providing a channel for immune cells to accumulate in the tumor.…”

Section: The Function Of Tlss In the Tmementioning

confidence: 99%

Tertiary Lymphoid Structures in Cancer: The Double-Edged Sword Role in Antitumor Immunity and Potential Therapeutic Induction Strategies

et al. 2021

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The complex tumor microenvironment (TME) plays a vital role in cancer development and dramatically determines the efficacy of immunotherapy. Tertiary lymphoid structures (TLSs) within the TME are well recognized and consist of T cell-rich areas containing dendritic cells (DCs) and B cell-rich areas containing germinal centers (GCs). Accumulating research has indicated that there is a close association between tumor-associated TLSs and favorable clinical outcomes in most types of cancers, though a minority of studies have reported an association between TLSs and a poor prognosis. Overall, the double-edged sword role of TLSs in the TME and potential mechanisms need to be further investigated, which will provide novel therapeutic perspectives for antitumor immunoregulation. In this review, we focus on discussing the main functions of TLSs in the TME and recent advances in the therapeutic manipulation of TLSs through multiple strategies to enhance local antitumor immunity.

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Section: The Function Of Tlss In the Tmementioning

confidence: 99%

Tertiary Lymphoid Structures in Cancer: The Double-Edged Sword Role in Antitumor Immunity and Potential Therapeutic Induction Strategies

et al. 2021

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“… 6 Angiogenesis is closely related to tumor progression and it makes tumors more prone to metastasis and recurrence; thus, highly vascularized NSCLC tends to be associated with a poor prognosis. 5 , 7 Currently, microvessel density (MVD) is the most commonly used indicator to evaluate angiogenesis. 8 In vasculogenic mimicry (VM), a tube surrounded by tumor cells lined with a periodic acid-Schiff (PAS)-positive basement membrane is formed.…”

Section: Introductionmentioning

confidence: 99%

The Relationship Between UBE2C and AGGF1 Overexpression and Tumor Angiogenesis in Non-Small Cell Lung Cancer

Wang¹,

Shi²,

Tao³

et al. 2021

CMAR

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Background Tumor infiltration and metastasis are the leading causes of death for patients with tumors. Angiogenesis is a prerequisite for tumor growth and metastasis. Angiogenic factor with G patch and FHA domains 1 (AGGF1) is an angiogenic factor, whereas ubiquitin-conjugating enzyme E2C (UBE2C) functions in protein ubiquitination. Microvessel density (MVD) is the most common indicator of tumor microvessels, and vasculogenic mimicry (VM) facilitates blood supply to tumors. This study explored UBE2C and AGGF1 expression in non-small cell lung cancer (NSCLC) and their relationship with angiogenesis and prognosis to identify biological factors that might predict NSCLC infiltration, metastasis, and prognosis. Methods The specimens and clinical pathological data of patients with NSCLC confirmed by pathology after surgical resection between January 2013 and December 2015 were collected. UBE2C and AGGF1 expression, as well as microvessel formation and VM in NSCLC, was observed using immunohistochemistry. The relationships between UBE2C, AGGF1, MVD, VM, and clinical pathological parameters and their relationships with overall survival (OS) and disease-free survival (DFS) were analyzed. Results UBE2C and AGGF1 levels in NSCLC tissues were significantly higher than those in corresponding normal tissues (57.1% vs 15.6 and 59.7% vs 25.3%, respectively; P < 0.05). UBE2C, AGGF1, MVD, and VM were positively correlated with each other ( P < 0.05) and were all related to tumor size, lymph node metastasis, and tumor-node-metastasis stage ( P < 0.05). Kaplan–Meier analysis showed that patient OS and DFS in the UBE2C, AGGF1, VM-positive, and high-MVD groups were reduced (all P < 0.001). Univariate and multivariate analyses showed that UBE2C, AGGF1, VM, and MVD were independent risk factors for NSCLC prognosis. Conclusion UBE2C and AGGF1 overexpression is associated with angiogenesis and poor prognosis and may be important for predicting NSCLC invasion, metastasis, and prognosis.

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“…NSCLC is a highly vascularized tumor and inhibition of angiogenesis has become a promising therapeutic approach [ 7 ]. It is reported that vascular endothelial growth factor (VEGF) plays an important role in the angiogenic signaling and vascular endothelial growth factor receptors (VEGFRs) are tyrosine kinases that serve as key regulators of this process.…”

Section: Introductionmentioning

confidence: 99%

Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer

Xie

Zhou

Liang

et al. 2021

J Exp Clin Cancer Res

102

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Background Recently, a variety of clinical trials have shown that apatinib, a small-molecule anti-angiogenic drug, exerts promising inhibitory effects on multiple solid tumors, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism of apatinib on NSCLC remains unclear. Methods MTT, EdU, AO/EB staining, TUNEL staining, flow cytometry, colony formation assays were performed to investigate the effects of apatinib on cell proliferation, cell cycle distribution, apoptosis and cancer stem like properties. Wound healing and transwell assays were conducted to explore the role of apatinib on migration and invasion. The regulation of apatinib on VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling were detected. Furthermore, we collected conditioned medium (CM) from A549 and H1299 cells to stimulate phorbol myristate acetate (PMA)-activated THP-1 cells, and examined the effect of apatinib on PD-L1 expression in macrophages. The Jurkat T cells and NSCLC cells co-culture model was used to assess the effect of apatinib on T cells activation. Subcutaneous tumor formation models were established to evaluate the effects of apatinib in vivo. Histochemical, immunohistochemical staining and ELISA assay were used to examine the levels of signaling molecules in tumors. Results We showed that apatinib inhibited cell proliferation and promoted apoptosis in NSCLC cells in vitro. Apatinib induced cell cycle arrest at G1 phase and suppressed the expression of Cyclin D1 and CDK4. Moreover, apatinib upregulated Cleaved Caspase 3, Cleaved Caspase 9 and Bax, and downregulated Bcl-2 in NSCLC cells. The colony formation ability and the number of CD133 positive cells were significantly decreased by apatinib, suggesting that apatinib inhibited the malignant and stem-like features of NSCLC cells. Mechanistically, apatinib inhibited PD-L1 and c-Myc expression by targeting VEGFR2/STAT3 signaling. Apatinib also inhibited PD-L1 expression in THP-1 derived macrophages stimulated by CM from NSCLC cells. Furthermore, apatinib pretreatment increased CD69 expression and IFN-γ secretion in stimulated Jurkat T cells co-cultured with NSCLC cells. Apatinib also promoted ROS production and inhibited Nrf2 and p62 expression, leading to the autophagic and apoptotic cell death in NSCLC. Moreover, apatinib significantly inhibited tumor growth in vivo. Conclusion Our data indicated that apatinib induced autophagy and apoptosis in NSCLC via regulating VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling.

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The Role of Anti-angiogenesis in the Treatment Landscape of Non-small Cell Lung Cancer – New Combinational Approaches and Strategies of Neovessel Inhibition

Cited by 34 publications

References 143 publications

Tertiary Lymphoid Structures in Cancer: The Double-Edged Sword Role in Antitumor Immunity and Potential Therapeutic Induction Strategies

Tertiary Lymphoid Structures in Cancer: The Double-Edged Sword Role in Antitumor Immunity and Potential Therapeutic Induction Strategies

The Relationship Between UBE2C and AGGF1 Overexpression and Tumor Angiogenesis in Non-Small Cell Lung Cancer

Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer

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