Remodeling of Tumor Immune Microenvironment by Oncolytic Viruses

Oncolytic viruses (OVs) are potential antitumor agents with unique therapeutic mechanisms. They possess the ability of direct oncolysis and the induction of antitumor immunity. OV can be genetically engineered to potentiate antitumor efficacy by remodeling the tumor immune microenvironment. The present mini review mainly describes the effect of OVs on remodeling of the tumor immune microenvironment and explores the mechanism of regulation of the host immune system and the promotion of the immune cells to destroy carcinoma cells by OVs. Furthermore, this article focuses on the utilization of OVs as vectors for the delivery of immunomodulatory cytokines or antibodies.

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RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4+ T-cell-dependent antitumor immunity

Nature Cancer ◽

10.1038/s43018-021-00263-z ◽

2021 ◽

Vol 2 (10) ◽

pp. 1018-1038

Author(s):

Zhuo Zhang ◽

Lin Luo ◽

Chuan Xing ◽

Yu Chen ◽

Peng Xu ◽

...

Keyword(s):

T Cell ◽

Antitumor Immunity ◽

Cd4 T Cell ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment

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An Oncolytic Adenovirus Armed with a Nanobody Against CD47 Reprograms Tumor Immune Microenvironment and Drives Durable Antitumor Immunity

SSRN Electronic Journal ◽

10.2139/ssrn.3914649 ◽

2021 ◽

Author(s):

Bin Zhang ◽

Yongheng Shu ◽

Shichuan Hu ◽

Zhongbing Qi ◽

Yanwei Chen ◽

...

Keyword(s):

Antitumor Immunity ◽

Oncolytic Adenovirus ◽

Immune Microenvironment ◽

Tumor Immune Microenvironment

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New Mechanisms of Tumor-Associated Macrophages on Promoting Tumor Progression: Recent Research Advances and Potential Targets for Tumor Immunotherapy

Journal of Immunology Research ◽

10.1155/2016/9720912 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 38

Author(s):

Qiujun Guo ◽

Zhichao Jin ◽

Yuan Yuan ◽

Rui Liu ◽

Tao Xu ◽

...

Keyword(s):

Tumor Microenvironment ◽

Poor Prognosis ◽

Antitumor Immunity ◽

Tumor Associated Macrophages ◽

Immune Microenvironment ◽

Comprehensive Review ◽

Tumor Immune Microenvironment ◽

Blocking Factors ◽

Macrophage Plasticity ◽

Poor Outcomes

The majority of basic and clinical studies have shown a protumor function of tumor-associated macrophages (TAMs), which represent a large proportion of matrix cells. TAMs promote tumorigenesis, and their number is related to the malignancy degree and poor prognosis of many kinds of tumors. Macrophage plasticity makes it possible to change the tumor microenvironment and remodel antitumor immunity during cancer immunotherapy. Increasing numbers of studies have revealed the effects of TAMs on the tumor microenvironment, for example, via promotion of tumor growth and tumorigenesis and through an increase in the number of cancer stem cells or via facilitation of angiogenesis, lymphangiogenesis, and metastasis. Investigators also proposed tumor-immunological treatments targeting TAMs by inhibiting TAM recruitment and differentiation, by regulating TAM polarization, and by blocking factors and pathways associated with the protumor function of TAMs. This comprehensive review presents recent research on TAMs in relation to prediction of poor outcomes, remodeling of the tumor immune microenvironment, and immunological targeted therapies.

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Interactions Between Anti-Vegf Therapy and Antitumor Immunity as a Potential Therapeutic Strategy in Colorectal Cancer

Acta Medica (Hradec Kralove Czech Republic) ◽

10.14712/18059694.2019.129 ◽

2019 ◽

Vol 62 (3) ◽

pp. 127-130

Author(s):

David Buka ◽

Josef Dvořák ◽

Igor Richter ◽

Pavel Škrobánek ◽

Tomáš Buchler ◽

...

Keyword(s):

Antitumor Immunity ◽

Checkpoint Inhibitors ◽

Therapeutic Interventions ◽

Successful Implementation ◽

Immune Microenvironment ◽

Combination Strategy ◽

Vessel Normalization ◽

Anti Vegf ◽

Tumor Immune Microenvironment ◽

General Response

There is a growing corpus of evidence indicating that anti-VEGF therapy may normalize the abnormal tumor vasculature with the potential to re-program the tumor immune microenvironment to a more immunosupportive profile. Tumor vessel normalization increases tumor perfusion, and, consequently, oxygen and nutrient supply, and thus can be assumed to improve the general response to anticancer immunotherapy. The increased antitumor immunity responses seen following anti-VEGF therapy may also be associated with the inhibition of the immunosuppressive action deployed by VEGF on effector T cells. Bearing in mind the recent advances of combination immunotherapy, combinations of anti-VEGF therapy with immune checkpoint inhibitors now appear to represent an attractive strategy. Key to the successful implementation of a combination strategy for treating cancer is understanding the interaction of these two therapeutic interventions, particularly in regards to appropriate reprogramming of the tumor immune microenvironment to improve antitumor immunity.

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Loss of Rnf43 accelerates Kras-mediated neoplasia and remodels the tumor immune microenvironment in pancreatic adenocarcinoma

10.1101/2021.05.29.446305 ◽

2021 ◽

Author(s):

Abdel Nasser Hosein ◽

Gita Dangol ◽

Takashi Okumura ◽

Jason Roszik ◽

Kimal Rajapakshe ◽

...

Keyword(s):

Catalytic Domain ◽

Affinity Maturation ◽

Genetically Engineered ◽

Ductal Adenocarcinoma ◽

Immune Microenvironment ◽

Cystic Neoplasms ◽

Genetically Engineered Mouse Model ◽

Conditional Expression ◽

Tumor Immune Microenvironment ◽

The Impact

RNF43 is an E3 ubiquitin ligase that is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC) and precursor cystic neoplasms of the pancreas. The impact of RNF43 mutations on PDAC is poorly understood and autochthonous models have not been sufficiently characterized. In this study we describe a genetically engineered mouse model (GEMM) of PDAC with conditional expression of oncogenic Kras and deletion of the catalytic domain of Rnf43 (KRC) in exocrine cells. We demonstrate that Rnf43 loss results in an increased incidence of high-grade cystic lesions of the pancreas and PDAC. Importantly, KRC mice have a significantly decreased survival compared to mice containing only an oncogenic Kras mutation. By use of single cell RNA sequencing we demonstrated that KRC tumor progression is accompanied by a decrease in macrophages, as well as an increase in T and B lymphocytes with evidence of increased immune checkpoint molecule expression and affinity maturation, respectively. This was in stark contrast to the tumor immune microenvironment observed in the Kras/Tp53 driven PDAC GEMM. Furthermore, expression of the chemokine, CXCL5, was found to be specifically decreased in KRC cancer cells by means of epigenetic regulation and emerged as a putative candidate for mediating the unique KRC immune landscape. This GEMM establishes RNF43 as a bona fide tumor suppressor gene in PDAC and puts forth a rationale for an immunotherapy approach in this subset of PDAC cases.

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Bioinorganic hybrid bacteriophage for modulation of intestinal microbiota to remodel tumor-immune microenvironment against colorectal cancer

Science Advances ◽

10.1126/sciadv.aba1590 ◽

2020 ◽

Vol 6 (20) ◽

pp. eaba1590 ◽

Cited By ~ 7

Author(s):

Xue Dong ◽

Pei Pan ◽

Di-Wei Zheng ◽

Peng Bao ◽

Xuan Zeng ◽

...

Keyword(s):

Colorectal Cancer ◽

Checkpoint Inhibitors ◽

Suppressor Cells ◽

In Vivo Studies ◽

Host Immune System ◽

Immune Microenvironment ◽

Phage Display Technology ◽

Tumor Immune Microenvironment

Mounting evidence suggests that the gut microbiota contribute to colorectal cancer (CRC) tumorigenesis, in which the symbiotic Fusobacterium nucleatum (Fn) selectively increases immunosuppressive myeloid-derived suppressor cells (MDSCs) to hamper the host’s anticancer immune response. Here, a specifically Fn-binding M13 phage was screened by phage display technology. Then, silver nanoparticles (AgNP) were assembled electrostatically on its surface capsid protein (M13@Ag) to achieve specific clearance of Fn and remodel the tumor-immune microenvironment. Both in vitro and in vivo studies showed that of M13@Ag treatment could scavenge Fn in gut and lead to reduction in MDSC amplification in the tumor site. In addition, antigen-presenting cells (APCs) were activated by M13 phages to further awaken the host immune system for CRC suppression. M13@Ag combined with immune checkpoint inhibitors (α-PD1) or chemotherapeutics (FOLFIRI) significantly prolonged overall mouse survival in the orthotopic CRC model.

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NIR-active Nanoterminator with Mature Dendritic Cell Acitivities for Immuno-Priming Mild Photothermal Cancer Therapy

10.26434/chemrxiv.12546698 ◽

2020 ◽

Author(s):

zhihong sun ◽

Guanjun Deng ◽

Xinghua Peng ◽

Xiuli Xu ◽

Lanlan Liu ◽

...

Keyword(s):

Dendritic Cell ◽

Photothermal Therapy ◽

Whole Body ◽

Mature Dendritic Cell ◽

Immune Microenvironment ◽

Highly Efficient ◽

Tumor Immune Microenvironment ◽

Shock Proteins ◽

Mild Temperature ◽

Broad Interest

Recently, photothermal-immuno synergistic therapy under mild temperature (~ 45 °C) has got broad interest in cancer treatment. Inhibition the intratumorally HSPs production is the key to accomplish highly efficient and mild photothermal therapy. In this work, we developed biomimetic nanoterminators with mature DCs functions by coating the mature dendritic cell membrane on photothermal nanoagents. As-prepared nanoterminators could automatically locate on T cell in the complex tumor-immune microenvironment and promote the T cells proliferation, activation and cytokine secretion, which could not only inhibit the expression of heat shock proteins to cooperate on highly efficient mild photothermal therapy (~42°C), but also promote tumor apoptosis during the treatment. More importantly, this nanoterminator could serve as vaccine to trigger anti-tumor immune response of the whole body, which would be promising to long-life tumor inhibition and termination.

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