Role of Nanoparticles in Cancer Immunotherapy
D. Sakthi Kumar, Aswathy Ravindran Girija in Bionanotechnology in Cancer, 2023
Though tumor immunosurveillance hypothesis emphasizes the ability of immune cells to recognize and eliminate cancer cells; however, many patients develop cancer even in the presence of an apparently normal immune system. This indicates that tumor cells are able to escape immune surveillance. To avoid attack from the immune system, tumor cells develop different strategies to escape immune surveillance. Cancer immune evasion is a major limitation for developing an effective therapeutic approach to treat cancer. To have a successful anticancer immune response, the tumor-immunity cycle should be circulated uninterrupted [24]. Blockade at any step in the pathway leads to unresponsiveness. Cancer cells develop different strategies to interrupt the tumor-immunity cycle. In below sections, we review different escape mechanisms employed by cancer cells.
Herpesvirus microRNAs for Use in Gene Therapy Immune-Evasion Strategies
Yashwant Pathak in Gene Delivery, 2022
Antibodies produced by non-self-antigens may compromise the recipient’s immune system cell survival after grafting. Immunosuppressive drugs may be required for the rest of the recipient’s life when receiving the graft.3 In addition to immune-evasion molecules, another approach that could reduce graft rejection is using DNA mutations. It is possible to subvert an immune response by expressing such molecules in the tissues of a graft. A virus in particular is extremely adept at manipulating the immune response of its hosts.1 The Herpes Simplex Virus (HSV) genome size and ability to be latent in neuronal cells make it unique for such gene delivery in the designated system, such as the nervous system, regarding its large genome size and for delivery of genes.1 The Herpesviridae family provides a reasonable proof of concept for this, since they have the ability to establish latency in the infected host and to persist for life. Many viral proteins involved in immune evasion have been characterized; however, the Herpesviridae also encode a large and diverse range number of viral microRNAs (miRNAs). Immune evasion is linked to some of them. Researchers have shown that several miRNAs inhibit the host’s immune system from destroying infected cells.4,5 In this chapter, miRNAs from some common herpesviruses that modulate immune responses will be discussed, culminating with a discussion of their potential application in non-immune generating cell therapy.
Herpes Simplex Virus Vaccines and the Viral Strategies Used to Evade Host Immunity
Marie Studahl, Paola Cinque, Tomas Bergström in Herpes Simplex Viruses, 2017
The studies discussed above establish that HSV-1 immune evasion molecules are important virulence factors. The question arises whether methods can be devised to block evasion activities mediated by these molecules. HSV-1 gC is expressed on the virus envelope and infected cell surface; therefore, gC is a potential target for vaccines that induce antibodies that bind to gC and block its immune evasion activities. Studies were performed in mice that were passively immunized with gC monoclonal antibodies prior to infection. Animals were protected against HSV-1 challenge by monoclonal antibodies that bind to the gC domain involved in C3b binding, but not by antibodies that recognize other regions on gC (69). Mice treated 1 or 2 days postinfection with gC monoclonal antibodies that block C3b binding also protected against virus challenge. Therefore, antibodies that target immune evasion domains can reduce the severity of infection.
Role of immune checkpoint inhibitors in the treatment of colorectal cancer: focus on nivolumab
Published in Expert Opinion on Biological Therapy, 2019
Alexandre A. Jácome, Cathy Eng
Immune evasion is one of the hallmarks of cancer [80]. These mechanisms remain to be fully elucidated, but it was demonstrated that tumor cells and tumor-infiltrating APCs express ligands of CTLA-4 and PD-1, such as B7-1, B7-2, and PD-L1, PD-L2, respectively. B7-1 and B7-2 are usually expressed by APCs, and their ligation to CD28 on T-cells is a co-stimulatory mechanism for lymphocyte activation [81,82]. CTLA-4 has a high affinity to B7-1 and B7-2, and acts as a negative stimulator by competitive inhibition. Similarly, the ligation of PD-L1 and PD-L2 to PD-1 directly regulates TCR signaling to attenuate T-cell signaling [83]. Another inhibitory role played by PD-L1 is through the interaction with B7-1 [84,85]. Expression of PD-1, as well as LAG3 and TIM3, is one of the markers of exhausted T cells [74].
Progesterone receptor promotes degradation of STAT2 to inhibit the interferon response in breast cancer
Published in OncoImmunology, 2020
Katherine R. Walter, Justin M. Balko, Christy R. Hagan
There is precedence for utilizing ubiquitination of STAT2 to inhibit type I interferon signaling. Multiple viruses employ viral proteins to function as E3 ubiquitin ligases to promote degradation of STAT2, thereby effectively inhibiting interferon signaling and allowing for the progression of infection.45–47 Much like viruses that need to overcome type I interferon signaling to replicate within their hosts, transformed cells need to downregulate or inhibit this pathway to avoid immune detection. Immune evasion allows for nascent tumor cells to avoid destruction by cytotoxic immune cells and progress to palpable tumors. Interestingly, mutations in STAT1 and STAT2 are not common in breast cancer.19 As the majority of breast cancers are PR-positive and our data have shown PR inhibits these pathways, genomic mutations of these proteins would not be necessary to establish an immunosuppressive, tumorigenic microenvironment; PR inhibition of STAT1 and STAT2 activity circumvents the need for loss/mutation of these proteins.
β-arrestin 2 quenches TLR signaling to facilitate the immune evasion of EPEC
Published in Gut Microbes, 2020
Zijuan Chen, Ruixue Zhou, Yihua Zhang, Doudou Hao, Yu Wang, Shichao Huang, Ningning Liu, Chunmei Xia, Nissan Yissachar, Feng Huang, Yiwei Chu, Dapeng Yan
Toll-like receptor 4 (TLR4) plays a pivotal role in early host defense against gram-negative bacteria. Upon ligand stimulation, TLR4 dimerizes and undergoes conformational change required for association of the adaptor protein myeloid differentiation primary response protein 88 (MyD88), which in turn recruits IL-1 R-associated kinase 4 (IRAK4) and IL-1 R-associated kinase 1 (IRAK1). Tumor necrosis factor receptor-associated factor 6 (TRAF6) is then recruited to the signal complex via interaction with phosphorylated IRAK1, which subsequently associates with the ubiquitin ligases ubiquitin-conjugating enzyme 13 and ubiquitin-conjugating enzyme E2 variant.12,13 This triggers K63-linked polyubiquitination of TRAF6 and the recruitment of transforming growth factor β-activated kinase (TAK1)/TAK1-binding protein 1/2 (TAB1/2) complex and induces TAK1 auto-phosphorylation.14 Activated TAK1 promotes the phosphorylation of mitogen-activated protein (MAP) kinases and inhibitor of nuclear factor-κB (IκB)-kinase (IKK), which ultimately leads to the expression of genes encoding cytokines and chemokines.15 Many studies have reported that pathogens had evolved a range of immune evasion strategies to establish a successful infection. Bacterial proteins can modulate key regulators in the TLR signaling pathway to affect the production of cytokines to promote the immune evasion.16,17 For example, Yersinia-secreted LcrV promotes IL-10 secretion in a CD14- and TLR2-dependant manner to suppress immune responses.18