In line with recent evidence, the development of cancer has been described as uncontrolled cell growth that results from gradual accumulation of genetic and epigenetic alterations, involving aberrations in oncogenes, tumor suppressor genes, and defects in genes engaged in DNA repair. As a result, cancer cells acquire a neoplastic phenotype and tumor-associated antigens (TAAs) are presented on their surface. These target structures should be recognized by cells of the immune system. However, a sequence of events at the genetic and epigenetic level disturb immune cells, and in consequence, make them unable to eliminate cancer cells.
Both innate and adaptive immunity are mobilized against cancer cells. In response to the appearance of cells with malignant transformation, NK cells release perforin and granzyme, causing direct cytolysis of the target cells. They can also secrete pro-inflammatory cytokines and in that way enhance the anticancer response. The activity of NK cells is regulated by a variety of activating and inhibitory receptors including NKG2D, KIR, CD94 -NKG2 heterodimers and natural cytotoxicity receptors, TNF family ligands, as well as co-stimulatory receptors, which recognize related molecules on target cells. A fundamental trigger of the anticancer immune response is the recognition of TAAs by T cells, via the major histocompatibility complex (MHC), which should be followed by signals from co-stimulatory molecules. Full activation of T lymphocytes requires a third signal provided by the presence of cytokines, and this leads to cell proliferation, differentiation, and secretion of chemokines and cytokines. The effect is to drive the clonal expansion of the T cells directed against TAAs and to recruit other immune effector cells in order to enhance immune defense.
Several mechanisms allow cancer cells to escape from immunological surveillance, including a) a loss of expression of MHC molecules, thus evading T cell recognition; b) a secretion of immunosuppressive cytokines, e.g., IL-10; c) an up-regulation of inhibitory molecules and an induction of a form of self-tolerance. The capacity of a host immune system to develop a response against cancer is unique to every individual person. The inter-individual differences in the susceptibility to cancer, cancer progression, and response to treatment may be modified by genetic and epigenetic factors.
An increasing body of evidence indicates that polymorphisms in genes encoding immunoregulatory molecules can be considered as low-risk modifiers for the susceptibility to develop different types of cancer, their progression rate and, most importantly, individual response to treatment. It was shown that polymorphisms in genes encoding key elements of adaptive immunity i.e. immune-checkpoint molecules (e.g. CTLA-4, PD-1), HLA, chemokines, cytokines as well as elements of innate immunity (e.g. KIRs or TLRs), can be associated with cancer risk and progression. However, no clear consensus exists over the genetic variations in genes encoding molecules related to the response to novel immunotherapies based on immune checkpoint blockade. Epigenetic alterations may, likewise, modify the anticancer host response. Recent work has detailed the role of specific epigenetic modifiers in the T cell response against cancer but there is still much to be learned about epigenetic control of the host response against cancer.
The purpose of this Research Topic is to collect novel information regarding genetic and epigenetic control on immune responses regulating molecules in cancer development, progression, and treatment. We welcome the submission of Reviews, Mini-Reviews, and Original Research articles covering subjects related to this field.
In line with recent evidence, the development of cancer has been described as uncontrolled cell growth that results from gradual accumulation of genetic and epigenetic alterations, involving aberrations in oncogenes, tumor suppressor genes, and defects in genes engaged in DNA repair. As a result, cancer cells acquire a neoplastic phenotype and tumor-associated antigens (TAAs) are presented on their surface. These target structures should be recognized by cells of the immune system. However, a sequence of events at the genetic and epigenetic level disturb immune cells, and in consequence, make them unable to eliminate cancer cells.
Both innate and adaptive immunity are mobilized against cancer cells. In response to the appearance of cells with malignant transformation, NK cells release perforin and granzyme, causing direct cytolysis of the target cells. They can also secrete pro-inflammatory cytokines and in that way enhance the anticancer response. The activity of NK cells is regulated by a variety of activating and inhibitory receptors including NKG2D, KIR, CD94 -NKG2 heterodimers and natural cytotoxicity receptors, TNF family ligands, as well as co-stimulatory receptors, which recognize related molecules on target cells. A fundamental trigger of the anticancer immune response is the recognition of TAAs by T cells, via the major histocompatibility complex (MHC), which should be followed by signals from co-stimulatory molecules. Full activation of T lymphocytes requires a third signal provided by the presence of cytokines, and this leads to cell proliferation, differentiation, and secretion of chemokines and cytokines. The effect is to drive the clonal expansion of the T cells directed against TAAs and to recruit other immune effector cells in order to enhance immune defense.
Several mechanisms allow cancer cells to escape from immunological surveillance, including a) a loss of expression of MHC molecules, thus evading T cell recognition; b) a secretion of immunosuppressive cytokines, e.g., IL-10; c) an up-regulation of inhibitory molecules and an induction of a form of self-tolerance. The capacity of a host immune system to develop a response against cancer is unique to every individual person. The inter-individual differences in the susceptibility to cancer, cancer progression, and response to treatment may be modified by genetic and epigenetic factors.
An increasing body of evidence indicates that polymorphisms in genes encoding immunoregulatory molecules can be considered as low-risk modifiers for the susceptibility to develop different types of cancer, their progression rate and, most importantly, individual response to treatment. It was shown that polymorphisms in genes encoding key elements of adaptive immunity i.e. immune-checkpoint molecules (e.g. CTLA-4, PD-1), HLA, chemokines, cytokines as well as elements of innate immunity (e.g. KIRs or TLRs), can be associated with cancer risk and progression. However, no clear consensus exists over the genetic variations in genes encoding molecules related to the response to novel immunotherapies based on immune checkpoint blockade. Epigenetic alterations may, likewise, modify the anticancer host response. Recent work has detailed the role of specific epigenetic modifiers in the T cell response against cancer but there is still much to be learned about epigenetic control of the host response against cancer.
The purpose of this Research Topic is to collect novel information regarding genetic and epigenetic control on immune responses regulating molecules in cancer development, progression, and treatment. We welcome the submission of Reviews, Mini-Reviews, and Original Research articles covering subjects related to this field.