1. Academic Validation
  2. SLAMF7 and TREM1 Mediate Immunogenic Cell Death in Colorectal Cancer Cells: Focus on Microsatellite Stability

SLAMF7 and TREM1 Mediate Immunogenic Cell Death in Colorectal Cancer Cells: Focus on Microsatellite Stability

  • Anticancer Res. 2021 Nov;41(11):5431-5444. doi: 10.21873/anticanres.15355.
Seon Ae Roh 1 Yi Hong Kwon 1 Jong Lyul Lee 1 2 Seon-Kyu Kim 3 Jin Cheon Kim 4 2
Affiliations

Affiliations

  • 1 Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
  • 2 Department of Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea.
  • 3 Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
  • 4 Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea; jckim@amc.seoul.kr.
Abstract

Background/aim: The aim of this study was to identify the association between SLAMF7 and TREM1 and anti-PD-1 drugs, and to determine whether they are molecular targets or predictors of responses to immunotherapy through induction of immunogenic cell death.

Materials and methods: CRC cell lines over-expressing SLAMF7 and TREM1 were used to examine immunogenic and biological traits (e.g., proliferation and invasiveness) associated with factors related to anti-cancer immunity. In addition, multiplex immunofluorescence was used to examine immune cells in microsatellite instability-high (MSI-H) CRC and microsatellite stable (MSS) CRC.

Results: Proliferation rate and invasiveness of TREM1-over-expressing CRC cells were significantly greater than those of control cells (p<0.001 and 0.031, respectively), whereas SLAMF7-over-expressing CRC cells showed the opposite traits (p=0.005 and 0.002, respectively). SLAMF7-over-expressing DLD-1 cells harboring MSI-H showed increased Apoptosis when treated with anti-PD-1 drugs, unlike SLAMF7-over-expressing SW480 cells harboring MSS. SLAMF7-over-expressing DLD1 and SW480 cells showed a marked increase in expression of the major cytokine mediator HMGB1 when exposed to anti-PD-1 drugs. Co-administration of anti-PD-1 drugs and TREM1 inhibitors induced Apoptosis only in MSI-H HCT116 cells; HMGB1 was over-expressed regardless of microsatellite status.

Conclusion: Expression of TREM1 and SLAMF7 is closely associated with immunogenic cell death, and TREM1 inhibitors may be an effective Adjuvant that enhances anti-PD-1-mediated immunogenic cell death in MSS CRC.

Keywords

Colorectal cancer; SLAMF7; TREM1; anti-PD1; immunogenic cell death; immunotherapy.

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