GEO series
Single cell profiling of peripheral blood mononuclear cells in diverse men with prostate cancer reveals lethal disease-associated immune signatures
GSE270387
Homo sapiens
Expression profiling by high throughput sequencing; Other
165 samples
Submitted 2026/07/24
Platform GPL24676
Summary
Purpose: Prostate cancer disproportionately affects men of African ancestry (AA), who also exhibit a distinct immunobiological profile. We aimed to investigate the composition and gene expression patterns of circulating peripheral blood mononuclear cells (PBMCs) in AA and European American (EA) prostate cancer patients, and to evaluate their association with ancestry and lethal prostate cancer outcomes. Experimental Design: We performed single-cell RNA sequencing (scRNA-seq) on 273,229 high-quality PBMCs isolated from 59 prostate cancer patients and healthy controls, along with single-cell TCR and BCR sequencing (scTCR-seq and scBCR-seq) in 53 individuals of African American (AA) and European American (EA) ancestry. Immune cell subpopulations were characterized, and differential gene expression and pathway analyses were conducted to identify ancestry-related differences and signatures associated with lethal disease. Results: Prostate cancer patients showed increased CD4⁺ cytotoxic and CD8⁺ effector memory T cells, with reduced CD4⁺ naïve and CD56 bright NK cells, indicating immune activation and dysregulation. AA patients had elevated CD4⁺ CTLs and cDC1s and fewer CD56 bright NK cells compared to EA. Lethal cases showed reduced cDC2s, suggestive of impaired immune priming. CD16⁺ monocytes shared 98 genes and 9 pathways across race and lethality contrasts, including enhanced interferon signaling in AA patients. Inflammatory and cytokine pathways—especially TNFα and NF-κB—were enriched in AA and in lethal disease, indicating shared immune dysregulation. TCR profiling revealed more large and hyperexpanded clonotypes in lethal cases, reflecting antigen-driven T cell responses and potential exhaustion. BCR sequencing showed reduced repertoire diversity and greater clonal dominance in lethal and EA patients, consistent with skewed humoral responses. Conclusions: Our findings reveal ancestry- and lethality-associated immune differences in prostate cancer. Elevated T cell exhaustion and inflammatory signaling in AA patients correlated with poor outcomes, highlighting potential ancestry-informed biomarkers and targets. Expanded T and B cell clones in lethal cases suggest antigen-driven immune activation with possible dysfunction.
This dataset
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Direct links to NCBI, no account and no request form: the whole study as GSE270387_RAW.tar, processed values as the series matrix, the supplementary file directory, and per-sample supplementary files for any of the 165 samples. Raw sequencing reads are also available from ENA.
Also filed as BioProject PRJNA1126289 and SRA study SRP515095. Searching any of these in the dataset finder brings you back here.
Study design
40 conditions, each sampled once — no replicated groups
Read from the first 40 of 165 sample titles: 40 distinct titles with little repetition. Check it against the sample list below before relying on it.
Samples in this study
0 selected
- GSM8341615 SCAF2311_1-28019
- GSM8341616 SCAF2312_2-27446
- GSM8341617 SCAF2314_4-27693
- GSM8341618 SCAF2316_6-28066
- GSM8341619 SCAF2317_3-27997
- GSM8341620 SCAF2318_5-28070
- GSM8341621 SCAF2779_21906
- GSM8341622 SCAF2780_22105
- GSM8341623 SCAF2781_22152
- GSM8341624 SCAF2782_23995
- GSM8341625 SCAF2783_24358
- GSM8341626 SCAF2784_24520
- GSM8341627 SCAF2785_25265
- GSM8341628 SCAF2786_25509
- GSM8341629 SCAF2805_21570
- GSM8341630 SCAF2806_22135
- GSM8341631 SCAF2807_22213
- GSM8341632 SCAF2808_22573
- GSM8341633 SCAF2809_25015
- GSM8341634 SCAF2810_26003
- GSM8341635 SCAF2811_26136
- GSM8341636 SCAF2812_27281
- GSM8341637 SCAF2817_21365
- GSM8341638 SCAF2818_21943
- GSM8341639 SCAF2819_22010
- GSM8341640 SCAF2820_22915
- GSM8341641 SCAF2821_23198
- GSM8341642 SCAF2822_24392
- GSM8341643 SCAF2823_24397
- GSM8341644 SCAF2824_24574
- GSM8341645 SCAF2858_22929
- GSM8341646 SCAF2871_22771
- GSM8341647 SCAF2872_24230
- GSM8341648 SCAF2873_25197
- GSM8341649 SCAF2874_26082
- GSM8341650 SCAF2875_26352
- GSM8341651 SCAF2876_26608
- GSM8341652 SCAF2877_27998
- GSM8341653 SCAF2916_22928
- GSM8341654 SCAF2917_22986
+ 125 more — browse all 165 samples with per-sample file links →
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