Cellular senescence and the tumour microenvironment

Abstract

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.

Comprehensive analysis of cellular senescence-related genes in the prognosis, tumor microenvironment, and immunotherapy/chemotherapy of clear cell renal cell carcinoma

“…The risk score characterized by distinct mutation profiles. cells (24). Therefore, CS-related genes may affect the TME.…”

Tieing together loose ends: telomere instability in cancer and aging

“…Telomere attrition to a critical threshold length that is no longer able to sustain telomere integrity is one of several known inducers of cellular senescence [50]. This type of senescence, termed telomere-induced or replicative senescence, can be triggered by the well-known tumour suppressor p53 and its downstream effector p21, a cyclin-dependent kinase inhibitor that represses the cell cycle (as discussed in an accompanying article in this special series [51,52]). Mathematical models and studies of budding yeast have suggested that the shortest telomeres are responsible for senescence induction [53,54].…”

“…Senescent cells secret specific small molecules or exosomes (EV) that interact with and influence the nearby environment. This phenomenon is known more generally as the Senescence-Associated Secretory Phenotype (SASP) and is a phenotype common to many senescent states, including that induced by eroded telomeres (please see accompanying review) [51,52,62,65,66] (Fig. 2).…”

The role of aging in cancer

“…Senescence-associated proliferation arrest and SASP cooperate in tumor suppression, by arresting proliferation of damaged pre-malignant cells and promoting immune clearance. Although senescence is acutely tumor suppressive, over the longer term, as a source of chronic inflammation, SASP also promotes tissue aging and disease, as reviewed by Rugang Zhang and colleagues [52] and Naoko Ohtani and colleagues [53].…”