Fig. 4: High IgG expression and NK activity are associated with improved outcomes.
In TCGA, plasma cell content and IgG expression were both higher in tumors with any IgG3 to 1 subclass switch recombination, a measure of B-cell clonality (a); Wilcoxon Rank Sum; n = 361 patients). We also show while high T-cell activity as represented by cytolytic activity was not associated with metastasis-free survival in JHMI, high IgG expression was associated with longer survival duration (b) (log-rank) even after adjusting for clinical covariates in Cox regression (c) (n = 300 patients; HR ± 95% confidence interval). Because plasma cells and IgG contribute to antibody-dependent cellular cytotoxicity in term of tumor immunogenicity which is classically defined by NK cell activity in response to IgG15,16, we noted in JHMI NK activity is elevated in tumors with high levels of plasma cells and IgG expression (d) (Wilcoxon Rank Sum; n = 300 patients). Within DVA, increasing plasma cells and IgG expression showed a continuous relationship between these scores and NK activity (e) (Kruskal–Wallis analyses for trend). Higher NK activity in JMHI trended towards an association with longer time to metastasis (f) (log-rank) which reached significance after adjusting for clinical covariates in Cox regression (g) (n = 300; HR ± 95% confidence interval). All survival estimations were performed using the Kaplan–Meier method. Asterisks next to p-values from Cox regressions denote statistical significance with p < 0.05. Box plots (a, d): center line, median; box limits, upper and lower quartiles; whiskers, 1.5x interquartile range. All P-values are two-sided. Abbreviations: JHMI Johns Hopkins Medical Institute, TCGA The Cancer Genome atlas, DVA Durham Veterans Affairs, HR Hazard ratio, PSA prostate-specific antigen.
