Journal article
Natural Killer Cell Infiltration in Prostate Cancers Predict Improved Patient Outcomes
Prostate cancer and prostatic diseases, Vol.28(1), pp.129-137
03/2025
DOI: 10.1038/s41391-024-00797-0
PMCID: PMC11349934
PMID: 38418892
Abstract
Natural killer (NK) cells are non-antigen specific innate immune cells that can be redirected to targets of interest using multiple strategies, although none are currently FDA-approved. We sought to evaluate NK cell infiltration into tumors to develop an improved understanding of which histologies may be most amenable to NK cell-based therapies currently in the developmental pipeline.
DNA (targeted/whole-exome) and RNA (whole-transcriptome) sequencing was performed from tumors from 45 cancer types (N = 90,916 for all cancers and N = 3365 for prostate cancer) submitted to Caris Life Sciences. NK cell fractions and immune deconvolution were inferred from RNA-seq data using quanTIseq. Real-world overall survival (OS) and treatment status was determined and Kaplan-Meier estimates were calculated. Statistical significance was determined using X
and Mann-Whitney U tests, with corrections for multiple comparisons where appropriate.
In both a pan-tumor and prostate cancer (PCa) -specific setting, we demonstrated that NK cells represent a substantial proportion of the total cellular infiltrate (median range 2-9% for all tumors). Higher NK cell infiltration was associated with improved OS in 28 of 45 cancer types, including (PCa). NK cell infiltration was negatively correlated with common driver mutations and androgen receptor variants (AR-V7) in primary prostate biopsies, while positively correlated with negative immune regulators. Higher levels of NK cell infiltration were associated with patterns consistent with a compensatory anti-inflammatory response.
Using the largest available dataset to date, we demonstrated that NK cells infiltrate a broad range of tumors, including both primary and metastatic PCa. NK cell infiltration is associated with improved PCa patient outcomes. This study demonstrates that NK cells are capable of trafficking to both primary and metastatic PCa and are a viable option for immunotherapy approaches moving forward. Future development of strategies to enhance tumor-infiltrating NK cell-mediated cytolytic activity and activation while limiting inhibitory pathways will be key.
Details
- Title: Subtitle
- Natural Killer Cell Infiltration in Prostate Cancers Predict Improved Patient Outcomes
- Creators
- Nicholas A Zorko - University of MinnesotaAllison Makovec - University of MinnesotaAndrew Elliott - Caris Life SciencesSamuel Kellen - University of MinnesotaJohn R Lozada - University of MinnesotaAli T Arafa - University of MinnesotaMartin Felices - University of MinnesotaMadison Shackelford - University of MinnesotaPedro Barata - University Hospitals Seidman Cancer CenterYousef Zakharia - University of IowaVivek Narayan - University of PennsylvaniaMark N Stein - Columbia University Irving Medical CenterKevin K Zarrabi - Sidney Kimmel Cancer CenterAkash Patnaik - University of ChicagoMehmet A Bilen - Emory UniversityMilan Radovich - Caris Life SciencesGeorge Sledge - Caris Life SciencesWafik S El-Deiry - Brown UniversityElisabeth I Heath - The Barbara Ann Karmanos Cancer InstituteDave S B Hoon - Saint John's Health CenterChadi Nabhan - Caris Life SciencesJeffrey S Miller - University of MinnesotaJustin H Hwang - University of MinnesotaEmmanuel S Antonarakis - University of Minnesota
- Resource Type
- Journal article
- Publication Details
- Prostate cancer and prostatic diseases, Vol.28(1), pp.129-137
- DOI
- 10.1038/s41391-024-00797-0
- PMID
- 38418892
- PMCID
- PMC11349934
- NLM abbreviation
- Prostate Cancer Prostatic Dis
- eISSN
- 1476-5608
- Grant note
- P01 CA065493 / NCI NIH HHS P30 CA077598 / NCI NIH HHS R35 CA283892 / NCI NIH HHS T32 GM008244 / NIGMS NIH HHS P01 CA111412 / NCI NIH HHS
- Language
- English
- Electronic publication date
- 02/28/2024
- Date published
- 03/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984563452902771
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