Natural Killer Cell Infiltration in Prostate Cancers Predict Improved Patient Outcomes.
Journal
Prostate cancer and prostatic diseases
ISSN: 1476-5608
Titre abrégé: Prostate Cancer Prostatic Dis
Pays: England
ID NLM: 9815755
Informations de publication
Date de publication:
28 Feb 2024
28 Feb 2024
Historique:
received:
08
10
2023
accepted:
22
01
2024
revised:
17
01
2024
medline:
29
2
2024
pubmed:
29
2
2024
entrez:
28
2
2024
Statut:
aheadofprint
Résumé
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 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.
Sections du résumé
BACKGROUND
BACKGROUND
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.
METHODS
METHODS
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
RESULTS
RESULTS
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.
CONCLUSIONS
CONCLUSIONS
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.
Identifiants
pubmed: 38418892
doi: 10.1038/s41391-024-00797-0
pii: 10.1038/s41391-024-00797-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIGMS NIH HHS
ID : T32 GM008244
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008244
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA283892
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA111412
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA077598
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA111412
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA065493
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA283892
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA065493
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA111412
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA077598
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA077598
Pays : United States
Informations de copyright
© 2024. The Author(s).
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