Mechanisms of Tumor Escape
Tumor Escape
The immune system is exceedingly essential in tumor therapy, in which the capacity of the immune system is restored for an efficient anti-tumor immune response to eliminate malignant cells. It has produced some clinical benefits in part of patients. Nonetheless, atypical tumor cells can evolve to fight back the immune system with various strategies to escape immune surveillance, proliferate rapidly, and transform as malignant cells. This treatment response tumor heterogeneity may reflect the ability of malignant cells to adapt to immune pressure through the loss of antigenicity and/or loss of immunogenicity as well as through the coordinating immunosuppressive microenvironment. The degree of the mechanisms of immune evasion may differ depending on the different types of tumors and even the tumor lesion. Therefore, based on the mechanisms of immune escape exploited by tumor cells, different strategies to enhance the efficacy of immunotherapy are required by restoring productive cancer immunosurveillance.
Mechanisms of Tumor Escape
Various mechanisms of the genetically unstable tumor to evade immune elimination have postulated, resulting in different altered tumor phenotypes. Tumor cells may lose their antigenicity and/or immunogenicity, also escape by orchestrating an immunosuppressive microenvironment. Loss of antigenicity may be achieved through the acquisition of defects in antigen processing and presentation of receptors involved in tumor antigen and through the loss of tumor antigens. The upregulation of key tolerogenic pathways could provide the tumor cells with additional immunosuppressive properties. Among them, expression of chemokines and secretion of suppressive cytokines, such as PD-L1, IL10, CD47, TGF-β, and VEGF, is increased to inhibit the immune cells and recruit immunosuppressive cells. This mechanism is essential in the inactivate effector T lymphocytes for the induction of functional inactivation and protects tumors from functional antitumor immune responses.
Fig.1 Immune escape mechanisms in cancer. (Beatty, 2015)
Some potent proinflammatory mediators such as IFNγ and TNF related apoptosis-inducing ligands and receptors are also related to immune evasion. Inhibitory signals and immune checkpoint receptors upregulated promote an immunosuppressive tumor environment. Furthermore, the absence of specific tumor antigen and the total or partial loss of MHC molecules is a widespread mechanism, due to the role of MHC antigens in antigen presentation to T-lymphocytes and the regulation of NK cell function. These losses make tumors more susceptible to NK immune effector mechanisms leading to the dysregulation of effector responses. These alterations play a crucial step in tumor development to escape destruction by hiding the recognition of the neoplastic cells from T-cells. The subsequently localized tumor microenvironment might inhibit tumor cell apoptosis and make tumor cells more resistant to the immune system.
Therefore, it is crucial for finding promising therapeutic strategies to survive and maintain the active functions within the immunosuppressive tumor environment, when drugs reach the tumor tissues. Based on the identification of tumor escape mechanisms, immunotherapy, which focuses on the boost of tumor-specific immunity and killing of tumor cells, has great promising and maybe more effective to help more patients get through specific diseases.
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References
- Beatty, G. L.; Gladney, W. L. Immune escape mechanisms as a guide for cancer immunotherapy. Clinical cancer research. 2015, 21(4), pp.687-692.
- Kunimasa, K.; Goto, T. Immunosurveillance and Immunoediting of Lung Cancer: Current Perspectives and Challenges. International Journal of Molecular Sciences. 2020, 21(2):597.