Targeting tumor vascularization: promising strategies for vascular normalization

Zheng, Rui; Li, Feifan; Gong, Aihua

doi:10.1007/s00432-021-03701-8

Cited by 44 publications

(28 citation statements)

References 122 publications

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“…Many studies have confirmed that OVs are powerful antiangiogenic agents that can significantly improve the hypoxic state of the TME. 14 However, whether OVs can achieve tumor VN remains to be further studied. To determine the effect of Ad-IL15 on tumor vessels, we collected tumor tissues from the B16-F10 model on day 7 after treatment.…”

Section: Resultsmentioning

confidence: 99%

“…However, clinical trials have shown various restrictions related to simple anti-vascular therapy, such as serious adverse reactions, drug resistance, reductions in blood perfusion, increases in tumor hypoxia, induction of vasculogenic mimicry (VM), and distant metastasis. 14 Therefore, pruning redundant vascular structures and stabilizing and remodeling abnormal vessels, to achieve vascular normalization (VN), have become new tumor treatment strategies. 15 Interestingly, the normal vascular system can enhance the antitumor immune response, 16 and enhanced immune responses also promote VN.…”

Section: Introductionmentioning

confidence: 99%

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

Hao

Lin

et al. 2022

OncoImmunology

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Inducing a full antitumor immune response in the tumor microenvironment (TME) is essential for successful cancer immunotherapy. Here, we report that an oncolytic adenovirus carrying mIL-15 (Ad-IL15) can effectively induce antitumor immune response and inhibit tumor growth in a mouse model of cancer. We found that Ad-IL15 facilitated the activation and infiltration of immune cells, including dendritic cells (DCs), T cells and natural killer (NK) cells, in the TME. Unexpectedly, we observed that Ad-IL15 also induced vascular normalization and tertiary lymphoid structure formation in the TME. Moreover, we demonstrated these Ad-IL15-induced changes in the TME were depended on the Ad-IL15-induced activation of the STING-TBK1-IRF3 pathway in DCs. Taken together, our findings suggest that Ad-IL15 is a candidate for cancer immunotherapy that promotes immune cell activation and infiltration, tumor vascular normalization and tertiary lymphoid structure formation in the TME.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Hao

Lin

et al. 2022

OncoImmunology

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“…This makes the vessels more mature, enhances the integrity of the tube wall, improves blood perfusion, and increases the oxygen partial pressure of the tumor tissue. The improvement of the hypoxic microenvironment makes tumor cells more sensitive to RT (28).…”

Section: Promoting the Synergistic Effects Of Rtmentioning

confidence: 99%

Candesartan induces tumor vascular normalization to improve the efficacy of radiotherapy in the therapeutic window

et al. 2022

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Background: This study sought to examine whether candesartan induces tumor vascular normalization in a narrow therapeutic window to increase perfusion and oxygen content, and thus enhance the effect of radiotherapy (RT). Methods: Candesartan was administered to tumor-bearing mice to induce the normalization of tumor vessels, and the time window for normalization was determined. Then, tumor vascular density, perfusion, pericyte coverage, hypoxia of tumor-bearing mice was detected at 3, 6, 9, 12 days, respectively. In the treatment window, RT was administered to enhance the anti-tumor effect, which was evaluated based on relevant anti-tumor indicators. The tumor volume and tumor weight were recorded. Next, tumor growth inhibition rate was calculated according to the tumor weight. The Tunnel and Ki-67 expression of the tumor tissues of every group was measured to evaluate the effects on tumor proliferation and apoptosis. Results: Based on tumor vascular density, perfusion, pericyte coverage, hypoxia, and other indicators, the tumor vascular normalization window occurred 9 days after the administration of candesartan. The antitumor results showed that administering RT during the therapeutic window enhanced anti-tumor efficacy, with a tumor growth inhibition rate of 66.67%. The results of Tunnel and Ki-67 expression showed that window-period RT significantly promoted tumor cell apoptosis and limited proliferation compared to the control group (P<0.05 in Tunnel expression and P<0.01 in Ki-67 expression). Conclusions: Candesartan regulates the normalization of tumor vessels and increases the sensitivity of RT in the therapeutic window.

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“…During tumor angiogenesis, the overexpression of pro-angiogenic factors results in the formation of irregular and tortuous vessels, which feature a discontinuous pericyte coverage, a high permeability [1,12] and a fenestrated basement membrane [13]. These features compromise the barrier integrity of the tumor vasculature and its perfusion, resulting in a sustained hypoxia, which may contribute to tumor maintenance and resistance to chemotherapy [14,15]. Connexins (Cx) form channels for the electrical and metabolic signaling, which coordinates the functions of individual cells [16,17], notably within the wall of blood vessels [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

Sathiyanadan

Alonso

Domingos-Pereira

et al. 2022

IJMS

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Connexin37 (Cx37) and Cx40 form intercellular channels between endothelial cells (EC), which contribute to the regulation of the functions of vessels. We previously documented the participation of both Cx in developmental angiogenesis and have further shown that loss of Cx40 decreases the growth of different tumors. Here, we report that loss of Cx37 reduces (1) the in vitro proliferation of primary human EC; (2) the vascularization of subcutaneously implanted matrigel plugs in Cx37−/− mice or in WT using matrigel plugs supplemented with a peptide targeting Cx37 channels; (3) tumor angiogenesis; and (4) the growth of TC-1 and B16 tumors, resulting in a longer mice survival. We further document that Cx37 and Cx40 function in a collaborative manner to promote tumor growth, inasmuch as the injection of a peptide targeting Cx40 into Cx37−/− mice decreased the growth of TC-1 tumors to a larger extent than after loss of Cx37. This loss did not alter vessel perfusion, mural cells coverage and tumor hypoxia compared to tumors grown in WT mice. The data show that Cx37 is relevant for the control of EC proliferation and growth in different tumor models, suggesting that it may be a target, alone or in combination with Cx40, in the development of anti-tumoral treatments.

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Targeting tumor vascularization: promising strategies for vascular normalization

Cited by 44 publications

References 122 publications

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

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

Candesartan induces tumor vascular normalization to improve the efficacy of radiotherapy in the therapeutic window

Targeting Endothelial Connexin37 Reduces Angiogenesis and Decreases Tumor Growth

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