American Association for Cancer Research
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FIGURE 5 from Siglec-15 Promotes Evasion of Adaptive Immunity in B-cell Acute Lymphoblastic Leukemia

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posted on 2023-07-17, 14:20 authored by Claire E. Pillsbury, Jodi Dougan, Jennifer L. Rabe, Jairo A. Fonseca, Chengjing Zhou, Alyssa N. Evans, Hasan Abukharma, Ona Ichoku, Gloria Gonzalez-Flamenco, Sunita I. Park, Ahmed Aljudi, Deborah DeRyckere, Sharon M. Castellino, Sarwish Rafiq, Solomon Langermann, Linda N. Liu, Curtis J. Henry, Christopher C. Porter

Sig15 is required for adaptive immune escape in murine B-ALL. qRT-PCR shows genetic knockdown of Siglec15 expression in a murine model of B-ALL by shRNA (shSig15; A) or knocked out using CRISPR/Cas9 (Sig15 KO; B). Data are normalized to the expression levels of a non-silencing vector control (shNS) or Cas9-expressing cells without gRNA (Cas9). C and D, Unirradiated WT or Rag1/ C57BL6 mice were injected via tail vein with 5 × 105 control or Sig15-deficient leukemia cells. Luciferase signal over time represents disease burden as measured via IVIS imaging over 14 days. Kaplan–Meier curve shows prolonged survival of WT recipients of Sig15-deficient leukemia. E,P < 0.0001; shNS WT versus shSig15 WT, Mantel–Cox log-rank test; n = 10 per group from two independent experiments. F,P < 0.0001, Cas9-only WT versus Sig15 KO WT; n = 10 per group from two independent experiments.


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Alex's Lemonade Stand Foundation for Childhood Cancer (ALSF)

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We demonstrate that Sig15 is overexpressed in hematologic malignancies driven by NFκB, is required for immune evasion in a mouse model of leukemia, and, for the first time, that it circulates at high levels in the plasma of children with leukemia.