American Association for Cancer Research
00085472can141752-sup-133136_2_supp_2843315_n9zk4s.pptx (219.79 kB)

Supplementary Figure 2 from CEACAM1-3S Drives Melanoma Cells into NK Cell-Mediated Cytolysis and Enhances Patient Survival

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posted on 2023-03-30, 23:30 authored by Nico Ullrich, Anja Heinemann, Elena Nilewski, Inka Scheffrahn, Joachim Klode, André Scherag, Dirk Schadendorf, Bernhard B. Singer, Iris Helfrich

Supplementary Figure 2. CEACAM1 isoforms also modulate surface expression of DNMA-1 ligands in an isoform specific mode of action.



CEACAM1 is a widely expressed multifunctional cell–cell adhesion protein reported to serve as a poor prognosis marker in melanoma patients. In this study, we examine the functional and clinical contributions of the four splice isoforms of CEACAM1. Specifically, we present in vitro and in vivo evidence that they affect melanoma progression and immune surveillance in a negative or positive manner that is isoform specific in action. In contrast with isoforms CEACAM1-4S and CEACAM1-4L, expression of isoforms CEACAM1-3S and CEACAM1-3L is induced during disease progression shown to correlate with clinical stage. Unexpectedly, overall survival was prolonged in patients with advanced melanomas expressing CEACAM1-3S. The favorable effects of CEACAM1-3S related to enhanced immunogenicity, which was mediated by cell surface upregulation of NKG2D receptor ligands, thereby sensitizing melanoma cells to lysis by natural killer cells. Conversely, CEACAM1-4L downregulated cell surface levels of the NKG2D ligands MICA and ULBP2 by enhanced shedding, thereby promoting malignant character. Overall, our results define the splice isoform-specific immunomodulatory and cell biologic functions of CEACAM1 in melanoma pathogenesis. Cancer Res; 75(9); 1897–907. ©2015 AACR.

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