CD38 in Advanced Prostate Cancers.
Adenosine pathway
B lymphocyte
CD38
Castration-resistant prostate cancer
Inflammation
Myeloid cell
Plasmacyte
Prostate cancer
T cell exhaustion
Tumour microenvironment
Journal
European urology
ISSN: 1873-7560
Titre abrégé: Eur Urol
Pays: Switzerland
ID NLM: 7512719
Informations de publication
Date de publication:
06 2021
06 2021
Historique:
received:
13
08
2020
accepted:
12
01
2021
pubmed:
9
3
2021
medline:
15
2
2022
entrez:
8
3
2021
Statut:
ppublish
Résumé
CD38, a druggable ectoenzyme, is involved in the generation of adenosine, which is implicated in tumour immune evasion. Its expression and role in prostate tumour-infiltrating immune cells (TIICs) have not been elucidated. To characterise CD38 expression on prostate cancer (PC) epithelial cells and TIICs, and to associate this expression with clinical outcomes. RNAseq from 159 patients with metastatic castration-resistant prostate cancer (mCRPC) in the International Stand Up To Cancer/Prostate Cancer Foundation (SU2C/PCF) cohort and 171 mCRPC samples taken from 63 patients in the Fred Hutchinson Cancer Research Centre cohort were analysed. CD38 expression was immunohistochemically scored by a validated assay on 51 castration-resistant PC (CRPC) and matching, same-patient castration-sensitive PC (CSPC) biopsies obtained between 2016 and 2018, and was associated with retrospectively collected clinical data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: mCRPC transcriptomes were analysed for associations between CD38 expression and gene expression signatures. Multiplex immunofluorescence determined CD38 expression in PC biopsies. Differences in CD38 CD38 mRNA expression in mCRPC was most significantly associated with upregulated immune signalling pathways. CD38 mRNA expression was associated with interleukin (IL)-12, IL-23, and IL-27 signalling signatures as well as immunosuppressive adenosine signalling and T cell exhaustion signatures. CD38 protein was frequently expressed on phenotypically diverse TIICs including B cells and myeloid cells, but largely absent from tumour epithelial cells. CD38 CD38 CD38 is expressed on the surface of white blood cells surrounding PC cells. These cells may impact PC growth and treatment resistance. Patients with PC with more CD38-expressing white blood cells are more likely to die earlier.
Sections du résumé
BACKGROUND
CD38, a druggable ectoenzyme, is involved in the generation of adenosine, which is implicated in tumour immune evasion. Its expression and role in prostate tumour-infiltrating immune cells (TIICs) have not been elucidated.
OBJECTIVE
To characterise CD38 expression on prostate cancer (PC) epithelial cells and TIICs, and to associate this expression with clinical outcomes.
DESIGN, SETTING, AND PARTICIPANTS
RNAseq from 159 patients with metastatic castration-resistant prostate cancer (mCRPC) in the International Stand Up To Cancer/Prostate Cancer Foundation (SU2C/PCF) cohort and 171 mCRPC samples taken from 63 patients in the Fred Hutchinson Cancer Research Centre cohort were analysed. CD38 expression was immunohistochemically scored by a validated assay on 51 castration-resistant PC (CRPC) and matching, same-patient castration-sensitive PC (CSPC) biopsies obtained between 2016 and 2018, and was associated with retrospectively collected clinical data. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: mCRPC transcriptomes were analysed for associations between CD38 expression and gene expression signatures. Multiplex immunofluorescence determined CD38 expression in PC biopsies. Differences in CD38
RESULTS AND LIMITATIONS
CD38 mRNA expression in mCRPC was most significantly associated with upregulated immune signalling pathways. CD38 mRNA expression was associated with interleukin (IL)-12, IL-23, and IL-27 signalling signatures as well as immunosuppressive adenosine signalling and T cell exhaustion signatures. CD38 protein was frequently expressed on phenotypically diverse TIICs including B cells and myeloid cells, but largely absent from tumour epithelial cells. CD38
CONCLUSIONS
CD38
PATIENT SUMMARY
CD38 is expressed on the surface of white blood cells surrounding PC cells. These cells may impact PC growth and treatment resistance. Patients with PC with more CD38-expressing white blood cells are more likely to die earlier.
Identifiants
pubmed: 33678520
pii: S0302-2838(21)00022-1
doi: 10.1016/j.eururo.2021.01.017
pmc: PMC8175332
pii:
doi:
Substances chimiques
RNA, Messenger
0
Adenosine
K72T3FS567
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
736-746Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Investigateurs
Dan Robinson
(D)
Eliezer M Van Allen
(EM)
Yi-Mi Wu
(YM)
Nikolaus Schultz
(N)
Robert J Lonigro
(RJ)
Juan-Miguel Mosquera
(JM)
Bruce Montgomery
(B)
Mary-Ellen Taplin
(ME)
Colin C Pritchard
(CC)
Gerhardt Attard
(G)
Himisha Beltran
(H)
Wassim Abida
(W)
Robert K Bradley
(RK)
Jake Vinson
(J)
Xuhong Cao
(X)
Pankaj Vats
(P)
Lakshmi P Kunju
(LP)
Maha Hussain
(M)
Scott A Tomlins
(SA)
Kathleen A Cooney
(KA)
David C Smith
(DC)
Christine Brennan
(C)
Javed Siddiqui
(J)
Rohit Mehra
(R)
Yu Chen
(Y)
Dana E Rathkopf
(DE)
Michael J Morris
(MJ)
Stephen B Solomon
(SB)
Jeremy C Durack
(JC)
Victor E Reuter
(VE)
Anuradha Gopalan
(A)
Jianjiong Gao
(J)
Massimo Loda
(M)
Rosina T Lis
(RT)
Michaela Bowden
(M)
Stephen P Balk
(SP)
Glenn Gaviola
(G)
Carrie Sougnez
(C)
Manaswi Gupta
(M)
Evan Y Yu
(EY)
Elahe A Mostaghel
(EA)
Heather H Cheng
(HH)
Hyojeong Mulcahy
(H)
Lawrence D True
(LD)
Stephen R Plymate
(SR)
Heidi Dvinge
(H)
Roberta Ferraldeschi
(R)
Penny Flohr
(P)
Susana Miranda
(S)
Zafeiris Zafeiriou
(Z)
Nina Tunariu
(N)
Joaquin Mateo
(J)
Raquel Perez-Lopez
(R)
Francesca Demichelis
(F)
Brian D Robinson
(BD)
Marc Schiffman
(M)
David M Nanus
(DM)
Scott T Tagawa
(ST)
Alexandros Sigaras
(A)
Kenneth W Eng
(KW)
Olivier Elemento
(O)
Andrea Sboner
(A)
Elisabeth I Heath
(EI)
Howard I Scher
(HI)
Kenneth J Pienta
(KJ)
Philip Kantoff
(P)
Johann S de Bono
(JS)
Mark A Rubin
(MA)
Peter S Nelson
(PS)
Levi A Garraway
(LA)
Charles L Sawyers
(CL)
Arul M Chinnaiyan
(AM)
Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.
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