Table 1.

Types of senescence and their roles within the tumor microenvironment

Type of senescence	Triggers	Role in TME	Mechanism	Senescent cell	Ref.
TIS	Chemotherapy Radiotherapy Targeted therapy	Anti-tumor	Immune surveillance by NK cells and macrophages	Tumor cell	7-9
			Complement activation	Tumor cell	10
			Recruitment of DCs and T cells	Tumor cell	7, 9
			Sensitization of chemotherapy and ICB in PDAC	Tumor cell	11
		Pro-tumor	Metastasis promotion	Tumor cell Fibroblast EC	8, 12, 13
			Invasion promotion	EC	12
			Stemness induction	Tumor cell	8
			Immunosuppression	CD8+ T cell Fibroblast	14-16
			Chemoresistance and EMT	Neutrophil Fibroblast	8, 17
			ICB resistance	Macrophage CD8+ T cell	18, 19
OIS	Oncogene activation	Anti-tumor	Recruitment of CD4+ T cells	Tumor cell EC	8, 20, 21
			Macrophage polarization towards M1	Fibroblast	22
		Pro-tumor	Tumorigenesis promotion	Macrophage Fibroblast	8, 23
			Metastasis promotion	Tumor cell EC	8, 13
			Invasion promotion	Tumor cell	8
			Chemoresistance	Tumor cell	8
			Immunosuppression	Fibroblast	8
SIPS	Stress signals	Pro-tumor	Tumorigenesis promotion(x2)	Fibroblast	24, 25
			Immunosuppression	Tumor cell	26
RS	Shortened telomere length	Pro-tumor	Angiogenesis	EC	27, 28
			Tumorigenesis promotion	Fibroblast	29
			Impaired immune surveillance	CD8+ T cell	30, 31
		Anti-tumor	Growth arrest	Tumor cell	32
Age-related immune dysfunction	Physiological aging	Pro-tumor	Macrophage polarization towards M2	Macrophage	33, 34
			Impaired immune surveillance	NK cell	35
			Metastasis promotion	Neutrophil	36
			Impaired antigen presentation	DC	37-39
			ICB adverse events	CD4+ T cell	40

TIS, therapy-induced senescence; OIS, oncogene-induced senescence; EC, endothelial cell; DC, dendritic cell; NK cell, natural killer cell; ICB, immune checkpoint blockade; PDAC, pancreatic ductal adenocarcinoma; EMT, epithelial-mesenchymal transition.