NK Cell Regulation in Cervical Cancer and Strategies for Immunotherapy

Abstract

Cervical cancer is one of the most prevalent gynaecological malignancies worldwide and is related to human papillomavirus (HPV) infection, viral persistence, progression, and invasion. Therefore, the immune response is linked to HPV status. Natural killer (NK) cells play a central role against virus-infected cells and tumours through a delicate balance between activating and inhibitory receptors and secretion of cytokines and chemokines. These cells also play a crucial role in tumour immunosurveillance. For these reasons, there is growing interest in harnessing NK cells as an immunotherapy for cervical cancer. These studies are diverse and include many strategies such as transferring activated autologous or allogeneic NK cells, improving the activation and cytolytic activity of NK cells using cytokines or analogues and modifying chimeric antigen receptors to increase specificity and targeting NK cells. However, research regarding the application of NK cells in immunotherapy is limited. This article focuses on recent discoveries about using NK cells to prevent and treat cervical cancer and the possibility of cellular immunotherapy becoming one of the best strategies to exploit the immune system to fight tumours.

m6A Regulator-Mediated Tumour Infiltration and Methylation Modification in Cervical Cancer Microenvironment

“…The m6Ascore was negatively associated with the abundance of activated CD4 + T cells, activated CD8 + T cells, activated dendritic cells, gdT cells, immature B cells, MDSCs, macrophages, mast cells, NK cells, Treg cells, Tfh cells, Th1 cells and Th2 cells. Studies have suggested that NK cells have a specific role in preventing HPV infection, the development and progression of cervical intraepithelial neoplasms and cancer of the uterine cervix (7). These observations were consistent with the role of T cells in immune surveillance to prevent HPV infection and consequent cancer reported previously (32).…”

“…T cells and mast cells have been suggested to be significantly associated with the survival rate of patients with cervical cancer (6). Human papillomavirus (HPV) infection and its oncoproteins help cervical tumour cells to evade attack by natural killer (NK) cells, while NK cells can recognise and eliminate cervical tumour cells and cells infected by the virus (7).…”

Cervical Cancer Prophylaxis—State-of-the-Art and Perspectives

“…An interesting phenomenon is the avoidance by CC tumor cells to the responses that NK cells are capable of causing. Among the numerous mechanisms, the one by which the secretion of cytokines necessary for NK cell activation is inhibited is noteworthy [ 23 ]. The ability of NK cells to eliminate CC cells represents a promising direction in the search for immunotherapy-based drugs.…”

Immunological Aspects of Human Papilloma Virus-Related Cancers Always Says, “I Am like a Box of Complexity, You Never Know What You Are Gonna Get”

“…Moreover, interferon gamma-inducible protein 16 (IFI16) is degraded by soluble E7 antigen and as a result IFN-γ decreases in the tumor microenvironment. Furthermore, production of a regulatory cytokine such as IL-10 and TGF-β induce MHC class I chain related-proteins A ( MICA ) and B ( MICB ), CD95 and inhibitory enzymes such as Indolamine-2,3-dioxygenase 1 (IDO), by tumor and regulatory cells suppress the activity of NK cells [ 73 ].…”

“…Thus, according to the importance of NK cells in the tumor microenvironment and tumor evasion, they are considered to be one of the valid candidates for HPV-related cancers. Autologous or allogeneic NK cells can be harnessed through gene manipulation, cytokine treatment for HPV-positive cancer immunotherapy [ 73 ].…”