Author: Katherine Chiappinelli

Publisher: Frontiers Media SA

Published: 2024-10-16

Total Pages: 299

ISBN-13: 2832555896

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.