Page 2202: In the article title, the phrase “tumor-immune microenvironment” should not have a hyphen.
Page 2205: The first sentence under “CD40L-mediated in vitro activation of CD70 expression in MCL cell lines” should read “Stable transduced Z138 SOX11-knockdown (Z138SOX11KD), JVM2 ectopically overexpressing SOX11 (JVM2SOX11+), and their respective control (Z138CT and JVM2CT) MCL cell line models, previously generated by our group,8,12 were used for in vitro experiments.”
Page 2209: In the first paragraph under “SOX11-mediated CD70 expression in MCL cells is activated by CD40L in vitro,” the sentence that begins “ChIP-qPCR” should read “ChIP-qPCR experiments showed fold enrichment of the CD70 locus in the ChIPs of SOX11+ cell line (Z138 wild type [WT] and JVM2SOX11+12 and Z138CT [red]) DNAs over their inputs, with a highly significant enrichment compared with non-SOX11-expressing cell lines (JVM2CT and Z138SOX11KD8 [blue]) (Figure 5A-B).”
There are corrections in some figures due to errors in figure processing during the publication process.
Page 2207: In Figure 4C, the blue and green data points should be red. In Figure 4G and H, some of the data points are the wrong color. In Figure 4G, part of a red data point should be visible just above the blue data point at the left end of the graph curve, and some adjacent data points in the graph should be slightly farther apart from each other. In Figure 4H, the data points and error bars for SOX11−, Ki67 low should be blue, not red; the red data points for SOX11+, Ki67 high should be green; the blue data points for SOX11+, Ki67 high should be red; and the upper four data points for SOX11−, Ki67 high should be green. In the legend to Figure 4, the references to purple and yellow data points in the description of panel G should refer to red and blue, respectively. In the description of panel H, “SOX11
+ and SOX11
− primary MCL cases” should read “SOX11
+ (red) and SOX11
− (blue) primary MCL cases” and “highlighted in red” should read “highlighted in green.” The corrected Figure 4 and its corrected legend are shown below.
Figure 4.
CD70 overexpression in nodal MCLs. (A) Venn diagram showing the overlap between the NanoString-based statistically significant upregulated genes in SOX11+ compared with SOX11− nodal MCLs (50 genes; blue circle) and SOX11+ compared with RLNs (54 genes; yellow circle). (B) Heatmap showing the scaled expression levels of common 24 significant upregulated genes in SOX11+ compared with SOX11− nodal MCLs and RLNs. Red represents increased expression and green reduced expression. Genes with an adjusted P value (Q-value) < .15 were considered. (C) CD70 mRNA expression levels in unpurified lymph node MCL samples (unpurified LN; n = 34), CD19+ purified cells from LN samples (CD19+ LN; n = 4) and peripheral blood samples (CD19+ PB; n = 15) (GSE70910). ∗q value < .05, ∗∗∗q value < .001. (D) Representative histological sections from (i) an RLN sample, (ii) SOX11+, and (iii) SOX11− nodal MCL biopsy, stained with specific anti-human CD70 antibody (×100). A double IHC staining with anti-human CD70 (brown) and (iv) anti-human cyclin D1 (red) antibodies (×100) was performed in the same SOX11− nodal MCL case as in (iii) to confirm the expression of CD70 by tumor cells (black arrows). Pictures contain insets with magnification (×400). (E) IHC quantifications of CD70+ cells in our series of SOX11+ (n = 51) and SOX11− (n = 13) nodal MCL primary samples. (F) IHC quantification of CD70 expression in nodal samples according to classic, blastoid/pleomorphic, or small cell MCL variants. (G) Positive correlation between CD70+ and Ki67+ cells, quantified by IHC in our series of nodal MCL. SOX11+ MCL are indicated in red, whereas SOX11− MCLs are in blue. Graphs show Pearson correlation coefficient (r), P value, and number of cases analyzed (N). (H) IHC quantification of CD70 expression in nodal MCL samples according to high (Ki67 >30%) and low (Ki67 ≤30%) proliferation rates in our series of SOX11+ (red) and SOX11− (blue) primary MCL cases. MCL cases diagnosed as blastoid/pleomorphic cytological variant are highlighted in green. The significance of differences was determined by independent samples Student t test: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001. (I) Kaplan-Meier curve and Cox regression showing the association of CD70+ cells, quantified by IHC using our series of SOX11+ nodal MCL primary samples (n = 40), with OS. (J) Kaplan-Meier curve and Cox regression showing the association of CD70 mRNA expression with OS, using previously published GEP from nodal samples and clinical data from 122 nodal SOX11+ MCL primary cases (GSE93291). High values were defined by Maxstat (cutoff point IHC = 25%, cutoff point mRNA = 9.9). Log-rank test P values, hazard ratios (HR) with 95% confidence interval (CI), and Cox regression P values are shown.
Figure 4.
CD70 overexpression in nodal MCLs. (A) Venn diagram showing the overlap between the NanoString-based statistically significant upregulated genes in SOX11+ compared with SOX11− nodal MCLs (50 genes; blue circle) and SOX11+ compared with RLNs (54 genes; yellow circle). (B) Heatmap showing the scaled expression levels of common 24 significant upregulated genes in SOX11+ compared with SOX11− nodal MCLs and RLNs. Red represents increased expression and green reduced expression. Genes with an adjusted P value (Q-value) < .15 were considered. (C) CD70 mRNA expression levels in unpurified lymph node MCL samples (unpurified LN; n = 34), CD19+ purified cells from LN samples (CD19+ LN; n = 4) and peripheral blood samples (CD19+ PB; n = 15) (GSE70910). ∗q value < .05, ∗∗∗q value < .001. (D) Representative histological sections from (i) an RLN sample, (ii) SOX11+, and (iii) SOX11− nodal MCL biopsy, stained with specific anti-human CD70 antibody (×100). A double IHC staining with anti-human CD70 (brown) and (iv) anti-human cyclin D1 (red) antibodies (×100) was performed in the same SOX11− nodal MCL case as in (iii) to confirm the expression of CD70 by tumor cells (black arrows). Pictures contain insets with magnification (×400). (E) IHC quantifications of CD70+ cells in our series of SOX11+ (n = 51) and SOX11− (n = 13) nodal MCL primary samples. (F) IHC quantification of CD70 expression in nodal samples according to classic, blastoid/pleomorphic, or small cell MCL variants. (G) Positive correlation between CD70+ and Ki67+ cells, quantified by IHC in our series of nodal MCL. SOX11+ MCL are indicated in red, whereas SOX11− MCLs are in blue. Graphs show Pearson correlation coefficient (r), P value, and number of cases analyzed (N). (H) IHC quantification of CD70 expression in nodal MCL samples according to high (Ki67 >30%) and low (Ki67 ≤30%) proliferation rates in our series of SOX11+ (red) and SOX11− (blue) primary MCL cases. MCL cases diagnosed as blastoid/pleomorphic cytological variant are highlighted in green. The significance of differences was determined by independent samples Student t test: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001. (I) Kaplan-Meier curve and Cox regression showing the association of CD70+ cells, quantified by IHC using our series of SOX11+ nodal MCL primary samples (n = 40), with OS. (J) Kaplan-Meier curve and Cox regression showing the association of CD70 mRNA expression with OS, using previously published GEP from nodal samples and clinical data from 122 nodal SOX11+ MCL primary cases (GSE93291). High values were defined by Maxstat (cutoff point IHC = 25%, cutoff point mRNA = 9.9). Log-rank test P values, hazard ratios (HR) with 95% confidence interval (CI), and Cox regression P values are shown.
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Page 2209: In Figure 5A and B, all of the graph bars should be red. In Figure 5C and D, the second bar from the left should be red with diagonal hatching, not blue; the third bar from the left should be solid blue, not red; and the rightmost bar should be blue with diagonal hatching, not solid blue. In the color key in Figure 5C, PBS should be represented by a white swatch and +CD40L should be represented by a swatch with diagonal hatching. In Figure 5D, the bottom halves of the error bars are missing. In the second sentence of the legend to Figure 5, "pb" should be "bp." The corrected Figure 5 and legend are shown below.
Figure 5.
SOX11-dependent CD70 expression is induced by CD40L in vitro in MCL cells. ChIP-qPCR experiments showing the enrichment of specific CD70 loci (1393-1119 bp upstream of the transcription start site), identified by SOX11 specific ChIP-chip experiments in (A) 2 SOX11+ MCL cell lines, Z138 wild-type (Z138WT) and JVM2SOX11+, and its control SOX11− MCL cell line (JVM2CT)12 and (B) in Z138 SOX11-knockdown (Z138SOX11KD) and its SOX11+ control (Z138CT) MCL cell line,8 were used for SOX11-specific ChIP-qPCRs experiments. DNA enrichment is displayed as fold change relative to its respective input chromatin and JVM2CT and Z138SOX11KD enrichment, respectively. (C) RT-qPCR quantification of CD70 mRNA levels (D) and FC quantification of CD70 protein expression levels analyzed in our stable transduced cell lines Z138CT/Z138SOX11KD incubated with vehicle (phosphate-buffered saline [PBS]) or 50 ng/mL CD40L, for 6 hours. Results are represented as fold change in CD40L-treated cells relative to PBS-treated cells. The significance of difference was determined by independent samples Student t test: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001.
Figure 5.
SOX11-dependent CD70 expression is induced by CD40L in vitro in MCL cells. ChIP-qPCR experiments showing the enrichment of specific CD70 loci (1393-1119 bp upstream of the transcription start site), identified by SOX11 specific ChIP-chip experiments in (A) 2 SOX11+ MCL cell lines, Z138 wild-type (Z138WT) and JVM2SOX11+, and its control SOX11− MCL cell line (JVM2CT)12 and (B) in Z138 SOX11-knockdown (Z138SOX11KD) and its SOX11+ control (Z138CT) MCL cell line,8 were used for SOX11-specific ChIP-qPCRs experiments. DNA enrichment is displayed as fold change relative to its respective input chromatin and JVM2CT and Z138SOX11KD enrichment, respectively. (C) RT-qPCR quantification of CD70 mRNA levels (D) and FC quantification of CD70 protein expression levels analyzed in our stable transduced cell lines Z138CT/Z138SOX11KD incubated with vehicle (phosphate-buffered saline [PBS]) or 50 ng/mL CD40L, for 6 hours. Results are represented as fold change in CD40L-treated cells relative to PBS-treated cells. The significance of difference was determined by independent samples Student t test: ∗P < .05, ∗∗P < .01, ∗∗∗P < .001.
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Page 2210: In Figure 6D and E, some of the red data points should be blue. In the figure legend, in the description of panels D and E, the references to red and blue data points are absent; in the description of panel F, “nodal MCL” should read “SOX11
+ nodal MCL.” The corrected Figure 6D and E and their corrected description in the figure legend are shown below.
Figure 6.
High number of intratumoral Treg cells correlates with high numbers of CD70+ cells in SOX11+ nodal MCLs, and it is associated with shorter OS of MCL patients. (D-E) Positive correlation between CD70+ cells and FOXP3+/CD4+ T-cell ratio (D) and CD70+ cells and (FOXP3+CTLA4+)/CD4+ T-cell ratio (E) in SOX11+ (red) and SOX11− (blue) nodal MCLs, quantified by IHC in our series of nodal MCLs. Graphs show Pearson correlation coefficient (r), P value, and number of cases analyzed (N).
Figure 6.
High number of intratumoral Treg cells correlates with high numbers of CD70+ cells in SOX11+ nodal MCLs, and it is associated with shorter OS of MCL patients. (D-E) Positive correlation between CD70+ cells and FOXP3+/CD4+ T-cell ratio (D) and CD70+ cells and (FOXP3+CTLA4+)/CD4+ T-cell ratio (E) in SOX11+ (red) and SOX11− (blue) nodal MCLs, quantified by IHC in our series of nodal MCLs. Graphs show Pearson correlation coefficient (r), P value, and number of cases analyzed (N).
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Page 2212: In Figure 7C, the blue squares (SOX11+, CD70 high) should be red and the red triangles (SOX11−, CD70 low) should be blue. The corrected Figure 7C is shown below.
Figure 7.
CD27 in MCLs. (C) Mean gray value (MGV) quantification of CD27 staining (see supplemental Methods) in cases with low and high CD70 expression.
Figure 7.
CD27 in MCLs. (C) Mean gray value (MGV) quantification of CD27 staining (see supplemental Methods) in cases with low and high CD70 expression.
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The publisher apologizes for these errors, which (except for changing “pb” to “bp” in the legend to Figure 5) have been corrected in the online version of the article.
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