title: Triggering Receptor Expressed on Myeloid Cells in Cutaneous Melanoma.
abstract: The tumor microenvironment plays an important role in the progression of melanoma, the prototypical immunologic cutaneous malignancy. The triggering receptor expressed on myeloid cells (TREM) family of innate immune receptors modulates inflammatory and innate immune signaling. It has been investigated in various neoplastic diseases, but not in melanoma. This study examines the expression of TREM-1 (a proinflammatory amplifier) and TREM-2 (an anti-inflammatory modulator and phagocytic promoter) in human cutaneous melanoma and surrounding tissue. Indirect immunofluorescence staining was performed on skin biopsies from 10 melanoma patients and staining intensity was semiquantitatively scored. Expression of TREM-1 and TREM-2 was higher in keratinocytes than melanoma tissue (TREM-1: p < 0.01; TREM-2: p < 0.01). Whereas TREM-2 was the dominant isoform expressed in normal keratinocytes, TREM-1 expression predominated in melanoma tissue (TREM-1 to TREM-2 ratio: keratinocytes = 0.78; melanoma = 2.08; p < 0.01). The increased TREM ratio in melanoma tissue could give rise to a proinflammatory and protumor state of the microenvironment. This evidence may be suggestive of a TREM-1/TREM-2 paradigm in which relative levels dictate inflammatory and immune states, rather than absolute expression of one or the other. Further investigation regarding this paradigm is warranted and could carry prognostic or therapeutic value in treatment for melanoma.
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Austin Huy
authors.initials: AH
authors.lastname: Nguyen
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Carleigh
authors.initials: C
authors.lastname: Koenck
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Shannon K
authors.initials: SK
authors.lastname: Quirk
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Victoria M
authors.initials: VM
authors.lastname: Lim
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Mario V
authors.initials: MV
authors.lastname: Mitkov
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Trowbridge
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Hunter
authors.affiliation: Center for Clinical and Translational Science, Creighton University School of Medicine, Omaha, Nebraska, USA.
authors.forename: Devendra K
authors.initials: DK
authors.lastname: Agrawal
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D015603:Keratinocytes / Q000737:chemistry* / Q000473:pathology; D008297:Male; D008545:Melanoma / Q000737:chemistry* / Q000473:pathology; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D011971:Receptors, Immunologic / Q000032:analysis*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000737:chemistry* / Q000473:pathology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D059016:Tumor Microenvironment
chemical_list: D014408:Biomarkers, Tumor; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; C498715:TREM2 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: Inflammation; TREM-1; TREM-2; melanoma; triggering receptor expressed on myeloid cells; tumor microenvironment