Oncolytic adenovirus: A tool for reversing the tumor microenvironment and promoting cancer treatment (Review)

Abstract

Immunogene therapy can enhance the antitumor immune effect by introducing genes encoding co-stimulation molecules, cytokines, chemokines and tumor-associated antigens into treatment cells or human cells through genetic engineering techniques. Oncolytic viruses can specifically target tumor cells and replicate indefinitely until they kill tumor cells. If combined with immunogene therapy, oncolytic viruses can play a more powerful antitumor role. The high pressure, hypoxia and acidity in the tumor microenvironment (TME) provide suitable conditions for tumor cells to survive. To maximize the potency of oncolytic viruses, various methods are being developed to promote the reversal of the TME, thereby maximizing transmission of replication and immunogenicity. The aim of the present review was to discuss the basic mechanisms underlying the effects of oncolytic adenoviruses on the TME, and suggest how to combine the modification of the adenovirus with the TME to further combat malignant tumors. Contents 1. Introduction 2. Oncolytic adenovirus 3. TME of solid tumors 4. Adenovirus modification combined with immune cells in the TME 5. Adenovirus modification combined with stromal cells in the TME 6. Adenovirus modification combined with immune checkpoints in the TME 7. Outlooks

Mutational profiling of low‐grade gliomas identifies prognosis and immunotherapy‐related biomarkers and tumour immune microenvironment characteristics

“…Immune checkpoints are regulatory molecules that play an inhibitory role in the immune system, 37 and they are essential for maintaining self-tolerance, preventing autoimmune response, and minimizing tissue damage by controlling the time and intensity of immune response. 38,39 The function of immune cells can be inhibited by the expression of immune checkpoint molecules on them, which makes the body unable to produce effective anti-tumour immune response, thus forming immune escape of tumours. 40 We found that the immune scores and immune checkpoint expression in CIC, IDH1 and ARID1A mutant group were obviously lower than that in wildtype, suggesting that the body can better recognize the mutated antigen cells and promote the immune function of T cells to better remove the antigen and inhibit tumour development.…”

“…In addition, we also found these six mutated genes were significantly correlated with the immune score and immune checkpoints. Immune checkpoints are regulatory molecules that play an inhibitory role in the immune system, 37 and they are essential for maintaining self‐tolerance, preventing autoimmune response, and minimizing tissue damage by controlling the time and intensity of immune response 38,39 . The function of immune cells can be inhibited by the expression of immune checkpoint molecules on them, which makes the body unable to produce effective anti‐tumour immune response, thus forming immune escape of tumours 40 .…”

Smart Oncolytic Adenovirotherapy to Induce Killing of Cancer Cells and Elicit Antitumor Immunity

“…However, many tumor cells are evolved to produce immune-inhibitory factors such as IL-10, TGF-β, and vascular endothelial growth factor (VEGF), which minimize the efficacy of the dendritic cells (Elmusrati et al, 2021, Farlow et al, 2021. Modifications of the adenovirus including the inclusion of a repressor for VEGF expression in the tumor cell could help promote dendritic cell efficacy and allow for increased immune response (Goradel et al, 2019, Wang, Zhong, et al, 2021.…”

“…Current research with smart oncolytic viruses focuses on two main hallmarks of cancer: the ability of cancer cells to evade the immune system and programmed cell death and their resistance to inhibitory signals preventing their growth (Wang, Zhong, et al, 2021). Multiple interconnected pathways between cancer and cells of the immune system converge in the development of a tumor environment where cancer cells can evade immune detection and programmed cell death (Huang et al, 2016).…”

“…These actions are usually counteracted by the production of immunosuppressive cells and cytokines by the tumor (Pardoll, 2012, Elmusrati et al, 2021. Immunostimulatory gene therapy focuses on tilting the suppressive tumor microenvrionment toward immune cell activation (Wang, Zhong, et al, 2021). Oncolytic viruses, and especially adenoviruses, have been demonstrated to be effective gene therapeutic vehicles for expressing immunostimulatory proteins within the tumor microenvironment to elicit antitumor immunity (Loskog, 2015, Wang, Xue, et al, 2021.…”