Fig. 1. Prostate tumour cells generate CXCR2 chemokines associated with tumour and peripheral myeloid inflammation.
a,b, Scatter plots of log-transformed intratumour CD11b+HLA-DRloCD15+CD14− cell density versus NLR (a) and neutrophil count (b) in patients with mCRPC (cohort 1, n = 48). Shown are estimated linear regression lines (pink) with 95% confidence intervals (grey), correlation coefficients, and P values from the two-sided Spearman’s rank correlation analyses. c, Micrograph showing a six-colour IF panel example of a human mCRPC biopsy stained for CD11b, HLA-DR, CD15, CD14 and CXCR2 and with DAPI, with arrows depicting different myeloid subsets. Scale bar, 100 μm. Entire slides were scanned and analysable slide areas were quantified for a,b. d, Volcano plot of the top 20 immune transcripts (green and pink) expressed in mCRPC biopsy bulk transcriptomes (RMH cohort, n = 95) that most positively associated with NLR. Pink, SASP genes and CXCR2 chemokines. e–g, Kaplan–Meier plots of overall survival from the time of CRPC biopsy based on gene expression of CXCL1 (e), CXCL2 (f) and CXCL8 (g) in CRPC bulk transcriptomes from the SU2C–PCF (n = 141) cohort. Gene expression cutoff was determined using the optimized Maxstat method. Blue line, low expression; red line, high expression. P values were calculated using the log-rank test. h, Violin plot of CXCR2 mRNA expression from single-cell RNA-seq data from 15 advanced prostate cancer biopsies (14 patients). TPM, transcripts per million; NK, natural killer; HSCs, haematopoietic stem cells. i, Violin plots by proportion of intratumour immune cell and tumour cells staining for CXCR2 protein in human mCRPC biopsies (n = 14). NE, neuroendocrine.