PT  - JOURNAL ARTICLE
AU  - SEON AE ROH
AU  - YI HONG KWON
AU  - JONG LYUL LEE
AU  - SEON-KYU KIM
AU  - JIN CHEON KIM
TI  - SLAMF7 and TREM1 Mediate Immunogenic Cell Death in Colorectal Cancer Cells: Focus on Microsatellite Stability
AID  - 10.21873/anticanres.15355
DP  - 2021 Nov 01
TA  - Anticancer Research
PG  - 5431--5444
VI  - 41
IP  - 11
4099  - http://ar.iiarjournals.org/content/41/11/5431.short
4100  - http://ar.iiarjournals.org/content/41/11/5431.full
SO  - Anticancer Res2021 Nov 01; 41
AB  - 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.