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. 2021 Jun 3;29:50–58. doi: 10.1016/j.euros.2021.05.002

Fig. 1.

Fig. 1

Patients with NMIBC exhibit sexual dimorphism in progression-free survival and tumor immune microenvironment. Kaplan-Meier survival curves showing female patients with high-grade NMIBC experienced significantly (p < 0.001) shorter PFS than their male counterparts and patients with low-grade tumors, in both (A) the UROMOL and (B) the KHSC cohorts. Kaplan-Meier survival analyses were performed using log-rank statistics with survival and survminer packages. (C) High-grade tumors from female patients in the UROMOL cohort exhibit significantly increased expression of immunoregulatory genes CXCL13, PDCD1, CD40, CTLA4, and ICOS. VST-normalized genes between four cohorts are as follows: high-grade cancer in females (HG_F), low-grade cancer in females (LG_F), high-grade cancer in males (HG_M), and low-grade cancer in males (LG_M). The Kruskal-Wallis test was employed to determine statistically significant differences. Violin plots of the mean cell counts for (D) CD163+ and (E) CD79a+ cell populations in the epithelial (left) and stromal (right) compartments of tumors from the KHSC cohort. Plots were stratified by low- and high-grade samples for males (blue) versus females (pink). Significant differences were signified by asterisks between grades (with bracket) and between sexes (no bracket), as determined by the Mann-Whitney U test. * p < 0.05. ** p < 0.01. *** p < 0.001. (F) In a subset of patients from the KHSC cohort that recurred in <1 yr, female patients had significantly higher density of CD163+ cells in the stroma and epithelium, while there were no significant sex-associated differences in CD79a+ cells. * p < 0.05. (G) Spearman correlation plot for CD163+, CD79a+, and PD-L1+ populations in the epithelial (Epi) and stromal (Str) compartments of tumors from the KHSC cohort. Dark blue indicates a positive correlation coefficient (>1), and dark red indicates a negative correlation coefficient (<1). (H) Violin plots of the mean cell counts for PD-L1+ cell populations in the epithelial (left) and stromal (right) compartments of tumors from the KHSC cohort. Plots were stratified by low- and high-grade samples for males (blue) versus females (pink). Differences between grades in each compartment were determined by the Mann-Whitney U test. *** p < 0.001. HG = high-grade; KHSC = Kingston Health Sciences Center; LG = low-grade; NMIBC = non–muscle-invasive bladder cancer; PFS = progression-free survival.