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

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 (MSIH) 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-overexpressing 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.

Automated summary

The study identified the association between SLAMF7 and TREM1 with anti-PD-1 drugs, and found that TREM1 inhibitors may enhance anti-PD-1-mediated immunogenic cell death in MSS CRC. The results showed that expression of SLAMF7 and TREM1 is closely associated with immunogenic cell death, providing insights into potential adjuvant therapies for CRC.