Immunosenescence and cancer predisposition in pediatric transplant recipients: An emerging paradigm

Figure 2 Context-dependent functions of the senescence-associated secretory phenotype in the tumour microenvironment. A: Tumour-suppressive senescence-associated secretory phenotype (SASP). In normal or premalignant tissues, senescent cells exert a tumour-suppressive effect by reinforcing the senescent state through SASP signals, which act in both an autocrine and paracrine manner. Through the secretion of SASP factors, these cells can recruit immune populations that recognize and eliminate them, a process known as senescence surveillance; B: Tumour-promoting SASP. In established or advanced tumours, however, SASP factors produced by senescent cells can instead foster tumour progression by stimulating angiogenesis, driving cancer cell proliferation, promoting epithelial-mesenchymal transition, and facilitating metastatic dissemination. Moreover, SASP components can dampen anti-tumour immune responses, thereby further supporting cancer growth. SASP: Senescence-associated secretory phenotype; IL: Interleukin; VEGF: Vascular endothelial growth factor; TGF-β: Transforming growth factor-β; CXCL1: Chemokine (C-X-C motif) ligand 1; CCL2: Chemokine (C-C motif) ligand 2; CCR2: C-C chemokine receptor 2; EMT: Epithelial-mesenchymal transition; MDSC: Myeloid-derived suppressor cells; ECM: Extracellular matrix; CKIa: Casein kinase Iα. Citation: Takasugi M, Yoshida Y, Ohtani N. Cellular senescence and the tumour microenvironment. Mol Oncol 2022; 16: 3333-3351. ©2022 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. This is an open access article under the terms of the http://creativecommons.org/Licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited (Supplementary material).