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Tytuł:
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SLAMF7 and TREM1 Mediate Immunogenic Cell Death in Colorectal Cancer Cells: Focus on Microsatellite Stability.
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Autorzy:
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Roh SA; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Kwon YH; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.
Lee JL; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea.; Department of Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Kim SK; Medical Genomics Research Center, Korea Research Institute of Bioscience & Biotechnology, Daejeon, Republic of Korea.
Kim JC; Asan Institute for Life Sciences, Asan Medical Center, Seoul, Republic of Korea; .; Department of Surgery, University of Ulsan College of Medicine, Seoul, Republic of Korea.
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Źródło:
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Anticancer research [Anticancer Res] 2021 Nov; Vol. 41 (11), pp. 5431-5444.
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Typ publikacji:
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Journal Article
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Język:
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English
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Imprint Name(s):
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Publication: Attiki, Greece : International Institute of Anticancer Research
Original Publication: Athens, Greece : Potamitis Press
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MeSH Terms:
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Cytotoxicity, Immunologic*
Microsatellite Instability*
Colorectal Neoplasms/*metabolism
Signaling Lymphocytic Activation Molecule Family/*metabolism
Triggering Receptor Expressed on Myeloid Cells-1/*metabolism
Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Apoptosis ; Cell Movement ; Cell Proliferation ; Coculture Techniques ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Gene Expression Regulation, Neoplastic ; HCT116 Cells ; HMGB1 Protein/genetics ; HMGB1 Protein/metabolism ; HT29 Cells ; Humans ; Immune Checkpoint Inhibitors/pharmacology ; Neoplasm Invasiveness ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Programmed Cell Death 1 Receptor/metabolism ; Signal Transduction ; Signaling Lymphocytic Activation Molecule Family/genetics ; THP-1 Cells ; Triggering Receptor Expressed on Myeloid Cells-1/antagonists & inhibitors ; Triggering Receptor Expressed on Myeloid Cells-1/genetics
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Contributed Indexing:
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Keywords: Colorectal cancer; SLAMF7; TREM1; anti-PD1; immunogenic cell death; immunotherapy
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Substance Nomenclature:
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0 (HMGB1 Protein)
0 (HMGB1 protein, human)
0 (Immune Checkpoint Inhibitors)
0 (PDCD1 protein, human)
0 (Programmed Cell Death 1 Receptor)
0 (SLAMF7 protein, human)
0 (Signaling Lymphocytic Activation Molecule Family)
0 (TREM1 protein, human)
0 (Triggering Receptor Expressed on Myeloid Cells-1)
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Entry Date(s):
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Date Created: 20211104 Date Completed: 20211115 Latest Revision: 20211115
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Update Code:
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20240105
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DOI:
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10.21873/anticanres.15355
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PMID:
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34732412
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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.
(Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)
