Fig 2: IGF2R expression with other clinical characteristics in the METABRIC datasets. (A) IGF2R expression in patients with TNBC and in other patients. (B) IGF2R expression in ER-negative patients and ER-positive patients. (C) IGF2R expression in HER2-positive patients and HER2-negative patients. (D) IGF2R expression in patients aged =60 years old and in patients aged >60 years old. (E) IGF2R expression in patients with chemotherapy and in patients without chemotherapy.

Fig 3: IGF2R expression association with CD8+ TILs and CD19+ TILs. (A, B) The patients with IGF2R-positive expression and a low percentage of CD8+ TILs. (C, D) The patients with IGF2R-negative expression and a high percentage of CD8+ TILs. (E, F) The patients with IGF2R-positive expression and a low percentage of CD19+ TILs. (G, H) The patients with IGF2R-negative expression and a high percentage of CD19+ TILs.

Fig 4: Induction of IGF2R expression in mouse CNS by L‐cycloserine and efficient uptake of a novel GALC‐AErbd fusion protein via an M6P‐independent pathway. A,B: Analysis of IFG2R expression in L‐cycloserine (L‐cys)‐treated and untreated twi mouse CNS. A: Representative sections from untreated (I–III) and L‐cys‐treated (IV–VI) twi mouse diencephalon. Hematoxylin and eosin (HE) staining (I, IV) shows no significant morphological differences between L‐cys‐treated and untreated mice. Immunohistochemical (IHC) staining (II, V) shows enhanced expression of IGF2R in L‐cys treated mouse diencephalon. To semiquantify expression of IGF2R in treated and untreated twi brain, the IHC‐stained sections were masked by red (3 + positive), orange (2 + positive), yellow (1 + positive), and blue (no signal; III, VI). All panels are X20. Scale bar = 100 µm. B: Semiquantification of IGF2R expression using IHC‐stained sagittal brain sections of L‐cys treated and untreated twi mice. Red and orange signals were quantified as positive cells. The percentage of positive cells between two groups were compared by two‐tailed Student's t‐test, N = 3 in each group, P = 0.006. C: Depiction of the lentiviral vectors used to characterize uptake of the novel GALC‐AErdb and its usage. ssp, Synthetic secretory signal peptide; psp, parental secretory signal peptide; co‐GALC, codon optimized mouse GALC cDNA; myc, myc tag; AErbd, ApoE receptor binding domain; 146gp91, myeloid‐specific promoter; IHK, erythroid/megakaryocyte‐specific promoter; WP, woodchuck hepatitis virus posttranscriptional regulatory element; ΔU3 LTR, SIN LTR deleted of the parental enhancer promoter. D: Uptake of GALC and GALC‐AErbd by 293T cells via the IGF2R and the LRP‐1 pathways. 293T cells were cultured either in the presence or in the absence of 1mM M6P (a competitive inhibitor of protein uptake via the IGF2R pathway) in conditioned media containing either GALC (generated by pTK1557‐transduced cells) or GALC‐AErbd (generated by pTK1664‐transduced cells). The GALC activity in these 293Tcells served as a surrogate marker for GALC uptake. Cellular GALC activity in the absence of M6P served as a reference value, considered to be 100%. The ratio of cellular GALC activity in the presence of M6P relative to GALC activity of the same protein without M6P was calculated. Uptake of GALC (pTK1557) was efficiently inhibited by the presence of 1 mM M6P, whereas uptake of the GALC‐AErbd fusion protein (pTK1664) was only slightly affected. E: Uptake of GALC and GALC‐AErbd by healthy and KD human fibroblasts cells via the IGF2R and the LRP‐1 pathways. Human fibroblasts isolated from healthy donors (Cont) and KD patients (Krabbe) were cultured either in the presence or absence of M6P (a competitive inhibitor of protein uptake via the IGF2R pathway) in conditioned media containing either GALC (generated by pTK1578‐transduced cells) or the GALC‐AErbd (generated by pTK1665‐transduced cells). The levels of GALC activity in naïve KD and healthy human fibroblasts are shown. Note that the presence of 2.5 mM M6P efficiently inhibited GALC uptake, whereas GALC‐AErbd uptake was not significantly affected in the presence of M6P.

Fig 5: Overall survival between the high- and low-risk patients in (A) the TCGA datasets and (B) the METABRIC, according to IGF2R expression.