A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway

Zhang, Chu-di; Wang, Yilong; Zhou, Dongming; Zhu, Man; Lv, Yao; Hao, Xiaoqiang; Qu, Chu-Fan; Chen, Yi; Gu, Weizhong; Wu, Benqing; Chen, Pei–Chun; Zhao, Zhengyan

doi:10.1016/j.tranon.2021.101091

Cited by 11 publications

(6 citation statements)

References 45 publications

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“…OVV, a new Cancer vaccine, can target tumor-specific antigens and may even induce novel tumor-specific T cell responses [24]. The oncolytic effect to CRC was demonstrated in some OVs such as Newcastle disease virus [25], and recombinant Chinese measles virus vaccine strain Hu191 [26]. These researches showed that OVs could induce apoptosis and inhibit cancer cell growth, but the inhibition effect in the different stages of CRC was not reported before.…”

Section: Discussionmentioning

confidence: 98%

Intestinal microbiota modulates the anti-tumor effect of oncolytic virus vaccine in colorectal cancer

Chen

Wang

Qin

et al. 2023

Preprint

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BackgroundImmunotherapy such as oncolytic virus has become a powerful cancer treatment but only a part of cancer patients can benefit from it, especially to advanced-stage cancer patients are required new therapeutic strategies to facilitate extended survival. Intestinal microbiota may contribute to colorectal cancer (CRC) carcinogenesis and response to immunotherapy. However, whether and how the modulating effect of intestinal microbiota on oncolytic virus vaccine (OVV) in CRC remains to be investigated.MethodsWe generated a MC38-gp33 CRC mouse model and treated with OVV-gp33 in early- and advanced-stages. Probiotics, fecal microbiota transplantation (FMT) and antibiotics (ABX) were treated to regulate the microbial composition of CRC mice of advanced stage. The tumor growth rate and survival time of mice were recorded. 16S rDNA sequencing analyzed the microbial composition and flow cytometry detected the T cells subsets activity.ResultsOVV-gp33 treatment led to inhibited tumor growth and prolonged survival in the early stage of CRC but did not have a significant effect on the advanced stage of CRC. Moreover, 16S rDNA sequence analysis and flow cytometry showed significant differences in intestinal microbiota composition, microbial metabolites and T-cell subsets in early- and advanced-stage CRC. Probiotic and FMT treatment significantly enhanced the antitumor effect of OVV in advanced stage of CRC with an increased abundance of activated CD8+T cells and a decreased ratio of Treg cells, while depletion of the microbiota by ABX eliminated the antitumor activity of OVV with decreased CD8+T-cell activation and upregulated Treg cells.ConclusionsThese results indicate that intestinal microbiota and microbial metabolites play an important role in the OVV antitumor effect in CRC, furthermore, altering the intestinal microbiota composition can modulate the antitumor and immunomodulatory effect of OVV in CRC.

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Section: Discussionmentioning

confidence: 98%

Intestinal microbiota modulates the anti-tumor effect of oncolytic virus vaccine in colorectal cancer

Chen

Wang

Qin

et al. 2023

Preprint

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“…In addition to direct oncolysis, OV induces ICD and elicits antitumor immunity. Recently, it has been reported that recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits the growth of human colorectal cancer by inducing autophagy and apoptosis via PI3K/Akt pathway ( Zhang et al., 2021 ). RGD (Arg-Gly-Asp)-modified oncolytic adenovirus carrying shPKM2 (M2 isoform of pyruvate kinase) (OAd.R.shPKM2) exhibits potent cytotoxicity in pancreatic cancer by inhibiting autophagy and promoting apoptosis ( Xu et al., 2017 ).…”

Section: Oncolytic Viruses-modulated Apoptosis Autophagy Syncytium Fo...mentioning

confidence: 99%

Oncolytic viruses-modulated immunogenic cell death, apoptosis and autophagy linking to virotherapy and cancer immune response

Sun²,

Chen

et al. 2023

Front. Cell. Infect. Microbiol.

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Recent reports have revealed that oncolytic viruses (OVs) play a significant role in cancer therapy. The infection of OVs such as oncolytic vaccinia virus (OVV), vesicular stomatitis virus (VSV), parvovirus, mammalian reovirus (MRV), human adenovirus, Newcastle disease virus (NDV), herpes simplex virus (HSV), avian reovirus (ARV), Orf virus (ORFV), inactivated Sendai virus (ISV), enterovirus, and coxsackievirus offer unique opportunities in immunotherapy through diverse and dynamic pathways. This mini-review focuses on the mechanisms of OVs-mediated virotherapy and their effects on immunogenic cell death (ICD), apoptosis, autophagy and regulation of the immune system.

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“…A recent study was concerned with the possibility of inducing autophagy in CRC by a novel oncolytic agent, namely recombinant Chinese measles virus vaccine strain Hu191 (rMV-Hu191), which also regulated PI3K/AKT signaling [ 251 ]. In HCT116 cells and in a mouse model, the induction of autophagy was demonstrated after treatment with W922, and this was also in the mechanism of inhibition of the PI3K/AKT/mTOR pathway [ 252 ].…”

Section: Autophagy and Igf System: Implications For Therapy In Crcmentioning

confidence: 99%

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia

Kasprzak

2023

IJMS

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Colorectal cancer (CRC) is one of the most common human malignancies worldwide. Along with apoptosis and inflammation, autophagy is one of three important mechanisms in CRC. The presence of autophagy/mitophagy in most normal mature intestinal epithelial cells has been confirmed, where it has mainly protective functions against reactive oxygen species (ROS)-induced DNA and protein damage. Autophagy regulates cell proliferation, metabolism, differentiation, secretion of mucins and/or anti-microbial peptides. Abnormal autophagy in intestinal epithelial cells leads to dysbiosis, a decline in local immunity and a decrease in cell secretory function. The insulin-like growth factor (IGF) signaling pathway plays an important role in colorectal carcinogenesis. This is evidenced by the biological activities of IGFs (IGF-1 and IGF-2), IGF-1 receptor type 1 (IGF-1R) and IGF-binding proteins (IGF BPs), which have been reported to regulate cell survival, proliferation, differentiation and apoptosis. Defects in autophagy are found in patients with metabolic syndrome (MetS), inflammatory bowel diseases (IBD) and CRC. In neoplastic cells, the IGF system modulates the autophagy process bidirectionally. In the current era of improving CRC therapies, it seems important to investigate the exact mechanisms not only of apoptosis, but also of autophagy in different populations of tumor microenvironment (TME) cells. The role of the IGF system in autophagy in normal as well as transformed colorectal cells still seems poorly understood. Hence, the aim of the review was to summarize the latest knowledge on the role of the IGF system in the molecular mechanisms of autophagy in the normal colon mucosa and in CRC, taking into account the cellular heterogeneity of the colonic and rectal epithelium.

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A recombinant Chinese measles virus vaccine strain rMV-Hu191 inhibits human colorectal cancer growth through inducing autophagy and apoptosis regulating by PI3K/AKT pathway

Cited by 11 publications

References 45 publications

Intestinal microbiota modulates the anti-tumor effect of oncolytic virus vaccine in colorectal cancer

Intestinal microbiota modulates the anti-tumor effect of oncolytic virus vaccine in colorectal cancer

Oncolytic viruses-modulated immunogenic cell death, apoptosis and autophagy linking to virotherapy and cancer immune response

Autophagy and the Insulin-like Growth Factor (IGF) System in Colonic Cells: Implications for Colorectal Neoplasia

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