Open AccessCellular senescence and the tumour microenvironment
Author(s) -
Takasugi Masaki,
Yoshida Yuya,
Ohtani Naoko
Publication year - 2022
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1002/1878-0261.13268
Subject(s) - senescence , stromal cell , tumor microenvironment , paracrine signalling , chemokine , biology , immune system , cancer cell , context (archaeology) , microbiology and biotechnology , cancer research , innate immune system , cancer , immunology , receptor , paleontology , genetics , biochemistry
The senescence‐associated secretory phenotype (SASP), where senescent cells produce a variety of secreted proteins including inflammatory cytokines, chemokines, matrix remodelling factors, growth factors and so on, plays pivotal but varying roles in the tumour microenvironment. The effects of SASP on the surrounding microenvironment depend on the cell type and process of cellular senescence induction, which is often associated with innate immunity. Via SASP‐mediated paracrine effects, senescent cells can remodel the surrounding tissues by modulating the character of adjacent cells, such as stromal, immune cells, as well as cancer cells. The SASP is associated with both tumour‐suppressive and tumour‐promoting effects, as observed in senescence surveillance effects (tumour‐suppressive) and suppression of anti‐tumour immunity in most senescent cancer‐associated fibroblasts and senescent T cells (tumour‐promoting). In this review, we discuss the features and roles of senescent cells in tumour microenvironment with emphasis on their context‐dependency that determines whether they promote or suppress cancer development. Potential usage of recently developed drugs that suppress the SASP (senomorphics) or selectively kill senescence cells (senolytics) in cancer therapy are also discussed.