Abstract
Introduction: Soluble CD27 (sCD27) is associated with somatic immune reaction status. Moreover, sCD27 level is associated with the prognosis of patients with prostate cancer who receive immunotherapy. Objective: In this study, we assessed sCD27 levels in patients with advanced lung cancer and determined their correlation with survival and clinicopathologic parameters. Methods: Serum samples were collected from patients with advanced lung cancer, and sCD27 was quantified via enzyme-linked immunosorbent assay. The association between sCD27 levels and clinicopathologic status and patient survival was retrospectively analyzed. Results: Of 96 patients analyzed, 73 had adenocarcinoma, 7 had squamous cell carcinoma, and 15 had small cell carcinoma. Median serum sCD27 level was 36.54 U/mL (range, undetectable–104.47); this is lower than that previously reported for patients with lung cancer, including those with localized stages. Patients with squamous cell carcinoma had higher sCD27 levels (p = 0.010). Age, performance status, and serum albumin levels were significantly correlated with serum sCD27 level. Patients with high serum sCD27 levels (≥32.52 U/mL; n = 58) had poorer prognosis than those with low serum sCD27 levels (<32.52 U/mL, n = 38; median survival, 7.3 vs. 21.8 months, respectively, p< 0.0001). Conclusions: High sCD27 level is associated with poor prognosis and may reflect the immune-exhausted status of patients with advanced lung cancer.
References
1.
van de Ven
K
, Borst
J
. Targeting the T-cell co-stimulatory CD27/CD70 pathway in cancer immunotherapy: rationale and potential
. Immunotherapy
. 2015
;7
(6
):655
–67
.
[PubMed]
1750-743X2.
Lens
SM
, Tesselaar
K
, van Oers
MH
, van Lier
RA
. Control of lymphocyte function through CD27-CD70 interactions
. Semin Immunol
. 1998
Dec
;10
(6
):491
–9
.
[PubMed]
1044-53233.
Font
J
, Pallares
L
, Martorell
J
, Martinez
E
, Gaya
A
, Vives
J
, et al. Elevated soluble CD27 levels in serum of patients with systemic lupus erythematosus
. Clin Immunol Immunopathol
. 1996
Dec
;81
(3
):239
–43
.
[PubMed]
0090-12294.
Goto
N
, Tsurumi
H
, Takemura
M
, Kanemura
N
, Kasahara
S
, Hara
T
, et al. Serum soluble CD27 level is associated with outcome in patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone
. Leuk Lymphoma
. 2012
Aug
;53
(8
):1494
–500
.
[PubMed]
1042-81945.
van Oers
MH
, Pals
ST
, Evers
LM
, van der Schoot
CE
, Koopman
G
, Bonfrer
JM
, et al. Expression and release of CD27 in human B-cell malignancies
. Blood
. 1993
Dec
;82
(11
):3430
–6
.
[PubMed]
0006-49716.
Nilsson
A
, de Milito
A
, Mowafi
F
, Winberg
G
, Björk
O
, Wolpert
EZ
, et al. Expression of CD27-CD70 on early B cell progenitors in the bone marrow: implication for diagnosis and therapy of childhood ALL
. Exp Hematol
. 2005
Dec
;33
(12
):1500
–7
.
[PubMed]
0301-472X7.
Jacobs
J
, Zwaenepoel
K
, Rolfo
C
, Van den Bossche
J
, Deben
C
, Silence
K
, et al. Unlocking the potential of CD70 as a novel immunotherapeutic target for non-small cell lung cancer
. Oncotarget
. 2015
May
;6
(15
):13462
–75
.
[PubMed]
1949-25538.
Wajant
H
. Therapeutic targeting of CD70 and CD27
. Expert Opin Ther Targets
. 2016
Aug
;20
(8
):959
–73
.
[PubMed]
1472-82229.
Okuma
Y
, Hosomi
Y
, Nakahara
Y
, Watanabe
K
, Sagawa
Y
, Homma
S
. High plasma levels of soluble programmed cell death ligand 1 are prognostic for reduced survival in advanced lung cancer
. Lung Cancer
. 2017
Feb
;104
:1
–6
.
[PubMed]
0169-500210.
Lausen
B
, Schumacher
M
. Maximally Selected Rank Statistics
. Biometrics
. 1992
Mar
;48
(1
):73
–85
. 0006-341X11.
Loenen
WA
, De Vries
E
, Gravestein
LA
, Hintzen
RQ
, Van Lier
RA
, Borst
J
. The CD27 membrane receptor, a lymphocyte-specific member of the nerve growth factor receptor family, gives rise to a soluble form by protein processing that does not involve receptor endocytosis
. Eur J Immunol
. 1992
Feb
;22
(2
):447
–55
.
[PubMed]
0014-298012.
Hintzen
RQ
, de Jong
R
, Hack
CE
, Chamuleau
M
, de Vries
EF
, ten Berge
IJ
, et al. A soluble form of the human T cell differentiation antigen CD27 is released after triggering of the TCR/CD3 complex
. J Immunol
. 1991
Jul
;147
(1
):29
–35
.
[PubMed]
0022-176713.
Law
CL
, Gordon
KA
, Toki
BE
, Yamane
AK
, Hering
MA
, Cerveny
CG
, et al. Lymphocyte activation antigen CD70 expressed by renal cell carcinoma is a potential therapeutic target for anti-CD70 antibody-drug conjugates
. Cancer Res
. 2006
Feb
;66
(4
):2328
–37
.
[PubMed]
0008-547214.
Yang
ZZ
, Novak
AJ
, Ziesmer
SC
, Witzig
TE
, Ansell
SM
. CD70+ non-Hodgkin lymphoma B cells induce Foxp3 expression and regulatory function in intratumoral CD4+CD25 T cells
. Blood
. 2007
Oct
;110
(7
):2537
–44
.
[PubMed]
0006-497115.
Wischhusen
J
, Jung
G
, Radovanovic
I
, Beier
C
, Steinbach
JP
, Rimner
A
, et al. Identification of CD70-mediated apoptosis of immune effector cells as a novel immune escape pathway of human glioblastoma
. Cancer Res
. 2002
May
;62
(9
):2592
–9
.
[PubMed]
0008-547216.
Pahl
JH
, Santos
SJ
, Kuijjer
ML
, Boerman
GH
, Sand
LG
, Szuhai
K
, et al. Expression of the immune regulation antigen CD70 in osteosarcoma
. Cancer Cell Int
. 2015
Mar
;15
(1
):31
.
[PubMed]
1475-286717.
Agathanggelou
A
, Niedobitek
G
, Chen
R
, Nicholls
J
, Yin
W
, Young
LS
. Expression of immune regulatory molecules in Epstein-Barr virus-associated nasopharyngeal carcinomas with prominent lymphoid stroma. Evidence for a functional interaction between epithelial tumor cells and infiltrating lymphoid cells
. Am J Pathol
. 1995
Oct
;147
(4
):1152
–60
.
[PubMed]
0002-944018.
Liu
N
, Sheng
X
, Liu
Y
, Zhang
X
, Yu
J
. Increased CD70 expression is associated with clinical resistance to cisplatin-based chemotherapy and poor survival in advanced ovarian carcinomas
. OncoTargets Ther
. 2013
Jun
;6
:615
–9
.
[PubMed]
1178-693019.
Hishima
T
, Fukayama
M
, Hayashi
Y
, Fujii
T
, Ooba
T
, Funata
N
, et al. CD70 Expression in Thymic Carcinoma.
Am J Surg Pathol 2000
. May;24(5):742–6. 20.
Chen
DS
, Mellman
I
. Oncology meets immunology: The cancer-immunity cycle. Immunity. 2013
Jul;35;39(1):1–10.21.
Hintzen
RQ
, Lens
SM
, Koopman
G
, Pals
ST
, Spits
H
, van Lier
RA
. CD70 represents the human ligand for CD27
. Int Immunol
. 1994
Mar
;6
(3
):477
–80
.
[PubMed]
0953-817822.
Coquet
JM
, Ribot
JC
, Bąbała
N
, Middendorp
S
, van der Horst
G
, Xiao
Y
, et al. Epithelial and dendritic cells in the thymic medulla promote CD4+Foxp3+ regulatory T cell development via the CD27-CD70 pathway
. J Exp Med
. 2013
Apr
;210
(4
):715
–28
.
[PubMed]
0022-100723.
Garon
EB
, Rizvi
NA
, Hui
R
, Leighl
N
, Balmanoukian
AS
, Eder
JP
, et al.; KEYNOTE-001 Investigators
. Pembrolizumab for the treatment of non-small-cell lung cancer
. N Engl J Med
. 2015
May
;372
(21
):2018
–28
.
[PubMed]
0028-479324.
Hellmann
MD
, Ciuleanu
TE
, Pluzanski
A
, Lee
JS
, Otterson
GA
, Audigier-Valette
C
, et al. Nivolumab plus Ipilimumab in Lung Cancer with a High Tumor Mutational Burden
. N Engl J Med
. 2018
May
;378
(22
):2093
–104
.
[PubMed]
0028-479325.
Fehrenbacher
L
, Spira
A
, Ballinger
M
, Kowanetz
M
, Vansteenkiste
J
, Mazieres
J
, et al.; POPLAR Study Group
. Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial
. Lancet
. 2016
Apr
;387
(10030
):1837
–46
.
[PubMed]
0140-673626.
Okuma
Y
, Wakui
H
, Utsumi
H
, Sagawa
Y
, Hosomi
Y
, Kuwano
K
, et al. Soluble Programmed Cell Death Ligand 1 as a Novel Biomarker for Nivolumab Therapy for Non-Small-cell Lung Cancer
. Clin Lung Cancer
. 2018
Sep
;19
(5
):410
–417.e1
.
[PubMed]
1525-730427.
Huang
J
, Jochems
C
, Anderson
AM
, Talaie
T
, Jales
A
, Madan
RA
, et al. Soluble CD27-pool in humans may contribute to T cell activation and tumor immunity
. J Immunol
. 2013
Jun
;190
(12
):6250
–8
.
[PubMed]
0022-1767© 2019 S. Karger AG, Basel
2019
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
