Table 2.
SASP factors that influence immune cell function in cancer.
| SASP Factor | Senescent Cells That Secrete Factor | Protumorigenic Mechanisms | Antitumorigenic Mechanisms | Reference |
|---|---|---|---|---|
| IL-6 | CD8+ T cells, B cells, macrophages | Recruit MDSCs, impair DC differentiation, inhibit antitumor T cell responses | Recruit macrophages and NKT cells | [231,232,233] |
| IL-8 | Tumor cells in solid tumors and hematological malignancies | Enhancement of angiogenesis, attraction of neutrophils and MDSCs | Reviewed in [234] | |
| IL-1α | Senescent fibroblasts. Breast cancer cells. Colon cancer cells | Regulation of IL-6 and IL-8 protumorigenic effects. Induction of production of tumor survival factors. Oncogene Ras-induced cell senescence, doxorubicin-induced cancer cell senescence and replicative senescence. |
Macrophage immune surveillance | [235,236,237,238] |
| IL-1β | Fibroblasts | Inflammaging, induction of ROS-mediated DDR | [58] | |
| IL-10 | Macrophages | Immunosuppression | [233] | |
| CXCL2/CXCR2 | Prostate cancer cells | T cell suppression through macrophage polarization to an anti-inflammatory phenotype. Recruit iMCs that hinder tumor cell senescence. |
[239,240] | |
| PGE2 | Hepatic stellate cells | Inhibit antitumor responses through PTGER4 receptor in hepatocellular carcinoma | [241] | |
| CCL2 | Senescent hepatocytes | Promotes accumulation of immunosuppressive iMCs promoting hepatocellular carcinoma through NK cell inhibition | Recruits myeloid cells that differentiate into macrophages to clear senescent precancerous cells | [39] |
| CCL3 (MIP-1 α) | Senescent hepatocytes | Recruit immune NK cells for clearance of senescent cells in hepatocellular carcinoma | [242] | |
| TGF-β1 | Fibroblasts | Inflammaging, induction of ROS-mediated DDR | [58] | |
| TGF-β3 | Senescent adipose-derived mesenchymal stem cells | Decreased angiogenic potential | [243] | |
| CCL5 | Melanoma cells | Recruit TILs to eliminate cancer cells | [244] | |
| TNFα | Induce T cell senescence | [109] | ||
| IFNγ | Bone marrow-derived macrophages | Induce M1 macrophage differentiation | [245] | |
| IFNα | Induce CD8+ T cell senescence, accelerates loss of CD27 and CD28 | [135] |
MDSC, myeloid-derived suppressor cell; NKT, natural killer T; TIL, tumor-infiltrating lymphocyte; iMC, Gr1+CD11b+ immature myeloid cell; DC, dendritic cell; IL, interleukin; PGE2, prostaglandin E2; TNF, tumor necrosis factor; IFN, interferon; ROS, reactive oxygen species; DDR, DNA damage response; CXCL, CXC-chemokine ligand; CXCR, CXC chemokine receptor; CCL, chemokine ligand; MIP; macrophage inflammatory protein; TGF, transforming growth factor; NK, natural killer