La senescenza nel microambiente tumorale

Abstract

Senescence is a complex biological process of gradual deterioration of cellular function over time in which cells stop dividing and have reduced functionality. In fact, senescent cells remain in a state of non-reactive cell cycle arrest although they preserve a metabolically active capacity of altering genetic and phenotypic characteristics as well as influencing the surrounding environment and adjacent cells. They are characterized by increased lysosomal activity and the acquisition of a bioactive secretome known as the senescence-associated secretory phenotype (SASP). The SASP phenotype consists of a variety of molecules, including, proinflammatory cytokines (IL-6, IL-8) chemokines, growth factors, angiogenic factors, proteases, extracellular matrix components, and metalloproteinases. The role of SASP in the tumor context is ambivalent because it seems that it protects cells from a pathological condition but also it contains a set of factors capable of inducing a neoplastic transformation. Cancer cells, in fact, can evade cell cycle control mechanisms, take advantage of senescence in order to survive and continue to proliferate, thus contributing to cancer progression. Furthermore, SASP can attract cells of the immune system to the site of senescence and T cells, indeed, assume a crucial role in the tumor microenvironment, supporting a delicate balance between immune response and promotion of tumor growth. Understanding these processes may provide new opportunities for the development of therapies that enhance the immune response against cancer and improve health in aging.