Page 121 - D. Cancer biology

The role of senescent tumor cells in colorectal cancer progression
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2,4
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Soon Sang Park , Ga-Yeon Lee , Young-Kyoung Lee , Young-Sam Kim , Tae-Gyu Kim , Yong Won Choi , Jang-Hee Kim and Tae
Jun Park 1,2,5
2
1 Department of Biochemistry and Molecular Biology, Ajou University School of Medicine; Department of Biomedical Sciences, Ajou University Graduate School of Medicine;
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3 Department of Hematology-Oncology, Ajou University School of Medicine; Department of Pathology, Ajou University School of Medicine;
5 Institute on Aging, Ajou University Medical Center, Suwon, 16499, Korea
Corresponding author : Tae Jun Park, park64@ajou.ac.kr
BACKGROUND AIM
Cellular senescence is historically considered to be an essential These findings suggest senescent tumor cells generate a
anticarcinogenic barrier in normal cells. Nonetheless, senescent cytokine barrier protecting non-senescent tumor cells from
tumor cells have been found not only in premalignant tumors but immune attack and provide a new target for overcoming the
also in developed malignant tumors. In a previous study, immunotherapy resistance of CRC.
senescent tumor cells play an important role in cancer
progression. This observation led to the hypothesis that
senescent tumor cells participate in immune cell infiltration.
METHODS
Fresh colorectal cancer tissue samples were obtained from patients. Immunohistochemistry, Senescence associated
β-galactosidase (SA-β-Gal) staining assay were performed to identify the presence of senescent tumor cells, Then
primary monocytes and CD8+ T cells isolation and activation Monocytes and CD8+ T cells were isolated from
human peripheral blood mononuclear cells (PBMCs), which were obtained from the Korean Redcross Blood
Services with the approval of the Institutional Review Board of Ajou University Hospital (AJIRB-BMR-SMP-17-424).
Ex vivo culture, chemotaxis assays and migration track were used to examine which type of SASP correlates with
the senescent tumor cells In Vitro. To verify it In Vivo, immune check point inhibitor treatment experiments were
performed along with the AOM/DSS-induced CRC mouse model.

RESULTS
Fig 1. Fig 2.

CONCLUSION REFERENCES ACKNOWLEDGEMENTS

In this study, we suggest another significant 1. Akishima-Fukasawa, Y. Prognostic This experiment was supported by National
role in cancer progression through immune significance of CXCL12 expression in Research Foundation of Korea to Tae Jun
suppression. In the battle between cancer patients with colorectal carcinoma. Am J Park at Ajou University (NRF-2019R1A2
and immune cells, senescent tumor cells Clin Pathol 132:202-210; quiz 307. (2009) C2086127, NRF-2020R1A6A1A03043539),
stand at the forefront of combat and form a
protective barrier, thereby inhibiting CD8+ T 2. Barreira da Silva, R. Dipeptidylpeptidase to Jang-Hee Kim at Ajou University (NRF-
cell infiltration and activation. Therefore, 4 inhibition enhances lymphocyte 2016R1D1A1B02010452) and to Yong Won
eliminating senescent tumor cells or trafficking, improving both naturally Choi at Ajou University (NRF-2018M3A9E8
targeting SASP is proposed as a new occurring tumor immunity and 023857, NRF-2018R1C1B6007847).
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