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Senescent Tumor Cells Build a Cytokine Shield in Colorectal Cancer

Authors
Choi, YW  | Kim, YH  | Oh, SY  | Suh, KW  | Kim, YS | Lee, GY | Yoon, JE | Park, SS | Lee, YK  | Park, YJ | Kim, HS | Park, SH | Kim, JH  | Park, TJ
Citation
Advanced science (Weinheim, Baden-Württemberg, Germany), 8(4). : 2002497-2002497, 2021
Journal Title
Advanced science (Weinheim, Baden-Württemberg, Germany)
ISSN
2198-3844
Abstract
Cellular senescence can either support or inhibit cancer progression. Here, it is shown that intratumoral infiltration of CD8+ T cells is negatively associated with the proportion of senescent tumor cells in colorectal cancer (CRC). Gene expression analysis reveals increased expression of C-X-C motif chemokine ligand 12 (CXCL12) and colony stimulating factor 1 (CSF1) in senescent tumor cells. Senescent tumor cells inhibit CD8+ T cell infiltration by secreting a high concentration of CXCL12, which induces a loss of CXCR4 in T cells that result in impaired directional migration. CSF1 from senescent tumor cells enhance monocyte differentiation into M2 macrophages, which inhibit CD8+ T cell activation. Neutralization of CXCL12/CSF1 increases the effect of anti-PD1 antibody in allograft tumors. Furthermore, inhibition of CXCL12 from senescent tumor cells enhances T cell infiltration and results in reducing the number and size of tumors in azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced CRC. These findings suggest senescent tumor cells generate a cytokine barrier protecting nonsenescent tumor cells from immune attack and provide a new target for overcoming the immunotherapy resistance of CRC.
Keywords

DOI
10.1002/advs.202002497
PMID
33643790
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Hematology-Oncology
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Pathology
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Ajou Authors
김, 영화  |  김, 장희  |  박, 태준  |  서, 광욱  |  오, 승엽  |  이, 영경  |  최, 용원
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