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ORIGINAL PAPER
Clinical and prognostic significance of PD-1 and PD-L1 expressionin sarcomas
Semra Paydas1 • Emine Kilic Bagir2 • Mehmet Ali Deveci3 • Gulfiliz Gonlusen2
Received: 26 June 2016 / Accepted: 6 July 2016 / Published online: 15 July 2016
� Springer Science+Business Media New York 2016
Abstract Programmed death-1 (PD-1) and programmed
death-ligand 1 (PD-L1) are new targets in cancer
immunotherapy in recent years. The aim of this study is to
evaluate the PD-1/PD-L1 expressions in sarcomas and to
determine association between PD-1/PD-L1 expressions
and clinical/pathological properties in some sarcoma sub-
types. Formalin-fixed, paraffin-embedded tissue samples
from 65 cases with sarcomas were analyzed. Immunohis-
tochemical staining was performed to detect the PD-1 and
PD-L1 expressions in tumor tissue and microenvironment,
separately. PD-1 expression in tumor tissue and microen-
vironment was detected in 11 (17 %) and 8 (12 %) cases,
respectively. PD-L1 expression in tumor tissue and
microenvironment was detected in 19 (29 %) and 20 cases
(30 %), respectively. None of the 5 Ewing sarcomas
involving bone showed PD-1/PD-L1 expression, while 2 of
3 cases with Ewing sarcomas involving soft tissue showed
PD-1 and PD-L1 expression. Among 5 cases with Kaposi
sarcoma, four showed PD-1 and/or PD-L1 expression in
tumor or microenvironment. PD-1/PD-L1 expressions were
detected 3 of 6 cases with pleomorphic sarcoma, 2 of 4
cases with peripheral nerve sheath tumors and 1 of 4 cases
with synovial sarcoma. Interestingly, strongest PD-1/PD-
L1 expressions in our study group were detected in 2 sar-
coma cases with the history of giant cell tumor. PD-1 and
PD-L1 expressions are up to 30 % of the cases with sar-
comas. It may be rational to target programmed death
pathway in Kaposi sarcoma, pleomorphic sarcoma and
peripheral nerve sheath tumors. Strong expression of PD-1/
PD-L1 in cases with previous giant cell bone tumor has
been found to be interesting and must be studied in giant
cell tumor samples.
Keywords PD-1 � PD-L1 � Immunotherapy � Sarcoma
Introduction
Immune checkpoints are cell surface molecules which are
endogenous regulators of the immune response. These
pathways are important in cancer and its microenvironment
and also in tumor escape from immune surveillance [1].
PD-1 is an inhibitory receptor that is part of the CD28
family and has a major role in tumor immune escape [2].
PD-L1 is the ligand for PD-1 and is expressed on T cells, B
cells, macrophages and dendritic cells. PD-L1 expression
has been found to be associated with poor prognosis in
some malignant tumors while non-prognostic in some
others [3–7].
Generally sarcomas are categorized as soft tissue and
bone sarcomas and represent heterogenous group of
malignancies with more than 70 distinct histologic sub-
types. Treatment of localized sarcomas is curative resec-
tion followed by adjuvant systemic therapy according to
the risk category. In advanced/metastatic disease, metas-
tasectomy, tumor debulking, radiation and chemotherapy
are frequently used strategies, but prognosis is poor in the
majority of these cases [8]. For this reason, immunotherapy
This study has been submitted to ESMO 2016 meeting.
& Semra Paydas
1 Department of Medical Oncology, Faculty of Medicine,
Cukurova University, Adana, Turkey
2 Department of Pathology, Faculty of Medicine, Cukurova
University, Adana, Turkey
3 Department of Orthopedics, Faculty of Medicine, Cukurova
University, Adana, Turkey
123
Med Oncol (2016) 33:93
DOI 10.1007/s12032-016-0807-z
will be an important choice in these cases. In fact, sarcomas
are among the first tumors to be considered for immune
manipulations since Coley’s experiments [9]. Here, we
explored the PD-1 and PD-L1 expressions in cases with
soft tissue and bone sarcomas and explored the association
between PD-1/PD-L1 expressions and clinical/histologic
features.
Patients and methods
Formalin-fixed, paraffin-embedded tissue samples from 65
cases with sarcomas were analyzed. Immunohistochemical
staining was performed to detect the PD-1 and PD-L1
expressions in tumor tissue and microenvironment. Five-
micrometer sections from sarcoma samples were used.
Monoclonal antibody MRQ-22, Ventana, was used to
detect PD-1 and CD274/PDL1 AM26531AF-N. Acris,
Germany, was used to detect PD-L1. The visualization
system used was the BenchMark XT with enzymatic
digestion (ISH protease 2, Ventana) and the iView Blue
Detection Kit (Ventana). Cases stained with anti-PD-1 and
PD-L1 were scored according to intensity of cytoplasmic
and/or membranous positivity as follows: 0 (no staining),
1? (weak or equivocal staining), 2? (moderate staining) or
3? (strong staining). Tumor cells and peritumoral
microenvironment were evaluated separately. Microenvi-
ronment positivity was considered when more than 5 %
population was stained.
Results
Among 65 cases, 15 had L-type sarcoma, 10 had
osteosarcoma, 6 had Ewing sarcoma, 2 had primitive
neuroectodermal tumor, 6 had pleomorphic sarcoma, 5 had
Kaposi sarcoma, 4 had peripheral nerve sheath tumor, 4
had synovial sarcoma, 3 had fibrosarcoma, and 10 cases
had other sarcomas. Totally, PD-1 expression in tumor
tissue and microenvironment was detected in 11 (17 %)
and 8 (12 %) cases, respectively. PD-L1 expression in
tumor tissue and microenvironment was detected in 19
(29 %) and 20 cases (30 %), respectively. In 15 L-type
sarcomas, PD-1 expression was not detected, and PD-L1
expression was detected in tumor and microenvironment in
2 cases and in only microenvironment in 1 case. In 10
osteosarcomas, in tumor tissue PD-L1 expression was
detected in three cases and PD-1 in two cases, and there
was no expression in microenvironment. None of the 5
Ewing sarcomas involving bone showed PD-1/PD-L1
expression, while 2 of 3 cases with Ewing sarcomas
involving soft tissue showed PD-1 and PD-L1 expression:
in one case PD-1 and PD-L1 in tumor and
microenvironment, and PD-1 only in one case. Among 5
cases with Kaposi sarcoma, four showed PD-1 and/or PD-
L1 expression: PD-1 in only one case in microenvironment
and PD-L1 in tumor or microenvironment in 4 cases. PD-1/
PD-L1 expressions were detected 3 of 6 cases with pleo-
morphic sarcoma, 2 of 4 cases with peripheral nerve sheath
tumors and 1 of 4 cases with synovial sarcoma. Interest-
ingly, strongest PD-1/PD-L1 expressions in our study
group were detected in 2 sarcoma cases with giant cell
tumor history. Clinical and histopathologic features and
PD-1/PD-L1 expressions in tumor and microenvironment
in different sarcoma subtypes are given in Tables 1, 2, 3, 4,
5, 6, 7 and 8. Figure 1 shows PD-1 and PD-L1 stainings in
different tumor types.
Discussion
PD-1 and its ligand PD-L1 play an important role in anti-
gen-specific T cell response mediating PD-1-dependent
immune suppression. The abnormal expression of these
ligands has been explored to understand their prognostic
value and also to determine the response to checkpoint
blocking therapies in many malignant tumors. However,
results are highly variable. On the other hand, prognostic
and/or predictive value of PD-1 and/or PD-L1 expressions
in tumors and their microenvironments including intratu-
moral lymphocytes and macrophages show more
heterogenous expressions [5, 6, 10–15].
In the present study, we looked for PD-1 and PD-L1
expressions in sarcomas both in tumor and in microenvi-
ronment and we found 17 and 12 % PD-1 expression and
29 and 30 % PD-L1 expression, respectively. Information
about PD-1/PD-L1 expressions in sarcomas is relatively
limited. The largest study about this matter covers 2539
sarcoma samples, DNA sequencing has been done, and PD-
L1 expression has been found in 50 % of the samples.
However, prognostic significance of this expression has not
been determined [16]. The most informative study covers
105 cases with soft tissue sarcomas. In this study, PD-1 (?)
lymphocytes and PD-L1 expression in tumor cells have
been detected in 65 and 58 % of the cases, respectively. In
this study, PD-1 expression has been found in all of the
cases with undifferentiated sarcoma and epithelioid sar-
coma. PD-L1 expression has been detected in the majority
of the cases with dedifferentiated liposarcoma, alveolar
rhabdomyosarcoma and angiosarcoma. Double expression
has been found in pleomorphic rhabdomyosarcoma,
angiosarcoma and undifferentiated sarcoma. More impor-
tantly, PD-1 and PD-L1 expressions have found to be
associated with advanced/metastatic stage disease, higher
grade, poorer differentiation and tumor necrosis and also
93 Page 2 of 10 Med Oncol (2016) 33:93
123
Table
1Clinicopathologic
variables,treatm
entdetails
andPD-1/PD-L1expressionin
L-typesarcomas
No
Histopathologic
subtype
Grade
Age
Sex
Localization
Tumor
diameter
Margin
Treatment
Metastasissite
PD-1
tumor
PD-1
ME
PD-L1
tumor
PD-L1
ME
PFS
OS
1De-differentiated
liposarcoma
LG
61M
Fem
ur
Multiple
Positive
MAID
Local
––
–?
26
58?
2De-differentiated
liposarcoma
43F
Retroperitoneum
89
69
2Positive
Metastaticin
diagnosis
––
??
–25
3De-differentiated
liposarcoma
LG
36F
Retroperitoneum
109
109
12
Positive
MAID
Local
––
––
19
42?
4De-differentiated
liposarcoma
48M
Scapula
?soft
tissue
249
189
15
Positive
MAID
Local
––
––
713?
5Myxoid
liposarcoma
IG57M
Maxillary
sinus
3.5
939
2Negative
MAID
Gem
–doce
Pazopanib
Local
––
––
29
35?
6Liposarcoma
78F
Retroperitoneum
249
129
7Positive
MAID
––
––
35
35?
7Leiomyosarcoma
HG
45F
Retroperitoneum
189
149
8Positive
MAID
Gem
–doce
Localablative
Liver,lung
––
––
721?
8Leiomyosarcoma
48F
Checum
109
8.5
96.5
Negative
MAID
at
relapse
Breastliver
––
––
72
91?
9Leiomyosarcoma
HG
68F
Mandibularsoft
tissue
??
MAID
Gem
–doce
Pazopanib
Lung
––
––
60
97?
10
Leiomyosarcoma
HG
49M
Humerus
99
49
4Negative
MAID
Gem
–doce
Tem
ozolomide
Locallung
––
––
15
51
11
Leiomyosarcoma
HG
47F
Humerus
109
49
4.5
Positive
MAID
––
??
26
26?
12
Leiomyosarcoma
STUMP
68F
Pelvic
mass
Negative
MAID
Liver
––
––
43
45?
13
Leiomyosarcoma
HG
63M
Cruris
7.5
92.5
92
Negative
MAID
––
––
99?
14
Leiomyosarcoma
HG
52F
Uterus
259
209
20
Negative
––
––
15
Leiomyosarcoma
HG
58M
Colon
139
129
10
Negative
MAID
––
––
17?
17?
Mmale,
Ffemale,
LG
low
grade,
IGinterm
ediate
grade,
HG
highgrade,
MEmicroenvironment,PFSprogressionfree
survival,OSoverallsurvival
Med Oncol (2016) 33:93 Page 3 of 10 93
123
Table
2Clinicopathologic
variables,treatm
entdetails
andPD-1/PD-L1expressionin
osteosarcomas
No
Histopathologic
subtype
Grade
Age
Sex
Localization
Tumor
diameter
Margin
Treatment
Metastasis
site
PD-1
tumor
PD-1
ME
PD-L1
tumor
PD-L1
ME
PFS
OS
1Osteosarcoma
27F
Fem
ur
––
––
2Osteosarcoma
21M
Fem
ur
189
89
18
Negative
HD
Mtx
Doxorubicin
Cisplatinum
––
––
–11?
11?
3Osteosarcoma
50F
Vertebra
79
59
5Positive
HD
Mtx
Doxorubicin
Cisplatinum
Localand
pelvic
––
?–
–17?
4Osteosarcoma
LG
60F
Fem
ur
169
89
6Negative
Doxorubicin
Cisplatinum
Gem
citabine–
docetaxel
Lung
––
––
16
19
5Osteosarcoma
19M
Fem
ur
229
229
15
Positive
Doxorubicin
Cisplatinum
Gem
citabine–
docetaxel
Lung
?–
?–
–15
6Osteosarcoma
HG
17M
Fem
ur
8.5
97.2
96
Positive
HD
Mtx
Doxorubicin
Lung
––
––
16
24
7Osteosarcoma
21M
Humerus
69
59
7Negative
HD
Mtx
Doxorubicin
––
––
–26?
26?
8Osteosarcoma
chondroblastic
28F
Vertebra
Metastatic
––
––
9OsteosarcomaGiant
cellrich
47F
Humerus
?–
?–
–10
10
Osteosarcoma
osteoblastic
23F
Tibia
Positive
––
––
6
Mmale,
Ffemale,
LG
low
grade,
IGinterm
ediate
grade,
HG
highgrade,
MEmicroenvironment,PFSprogressionfree
survival,OSoverallsurvival
93 Page 4 of 10 Med Oncol (2016) 33:93
123
Table
3Clinicopathologic
variables,treatm
entdetails
andPD-1/PD-L1expressionin
Ewingsarcomas
No
Histopathologic
subtype
Age
Sex
Localization
Tumor
diameter
Margin
Treatment
Metastasissite
PD-1
tumor
PD-1
ME
PD-L1
tumor
PD-L1
ME
PFS
OS
1Ewingsarcoma
24M
Tibia
159
10
Negative
EVAIA
––
––
–16?
16?
2Ewingsarcoma
28M
Scapula
10.7
913.6
Nosurgery
EVAIA
Lungleptomeninx
––
––
27
30
3Ewingsarcoma
32M
Iliacbone
199
14
Nosurgery
EVAIA
Gem
–doce
trabectedin
Lungbone
––
––
10
29?
4Ewingsarcoma
46F
Gluteus
10.5
99.5
Nosurgery
EVAIA
––
––
9
5Ewingsarcoma
25M
––
––
6Ewingsarcoma
19F
Fem
ur
189
49
5Negative
EVAIA
Bone
Central
nervous
system
––
––
24
27
7Ewingsarcoma
76M
Retroperitoneum
209
30
Nosurgery
EVAIA
Metastaticdisease
at
diagnosis
??
??
–14
8Ewingsarcoma
18F
Bladder
109
79
7Negativeafter
chem
otherapy
Metastaticdisease
at
diagnosis
??
––
132?
132?
Mmale,
Ffemale,
LG
low
grade,
IGinterm
ediate
grade,
HG
highgrade,
MEmicroenvironment,PFSprogressionfree
survival,OSoverallsurvival
Table
4Clinicopathologic
variables,treatm
entdetails
andPD-1/PD-L1expressionin
peripheral
nervesheath
tumor
No
Histopathologic
subtype
Grade
Age
Sex
Localization
Tumor
diameter
Margin
Treatment
Metastasis
site
PD-1
tumor
PD-1
ME
PD-L1
tumor
PD-L1
ME
PFS
OS
1Peripheral
nervesheath
tumor
LG
61F
Gluteus
79
69
5Negative
MAID
Gem
–doce
Tem
ozolomide
Liver
lung
––
––
14
49
2Peripheral
nervesheath
tumor
HG
85F
Radius
49
39
3Positive
MAID
–?
–?
24?
24?
3Peripheral
nervesheath
tumor
HG
65F
Fem
ur
49
39
4Positive
MAID
Gem
–doce
Lung
––
––
8
4Peripheral
nervesheath
tumor
HG
44M
Popliteal
region
129
12
Negative
MAID
Gem
–doce
Pazopanib
Lung
Liver
??
????
?6
38?
Mmale,
Ffemale,
LG
low
grade,
IGinterm
ediate
grade,
HG
highgrade,
MEmicroenvironment,PFSprogressionfree
survival,OSoverallsurvival
Med Oncol (2016) 33:93 Page 5 of 10 93
123
shorter disease-free/overall survival times [17]. In our
study group, there were 4 cases with dedifferentiated
liposarcoma; none showed PD-1 expression, and 2 showed
PD-L1 in tumor and/or microenvironment. In another study
covering 50 cases with soft tissue sarcomas using DAKO
PD-L1 immunohistochemistry and [1 % of tumor cells
staining cutoff, PD-L1 expression has been detected in only
12 % of the sarcomas with the majority being gastroin-
testinal stromal tumors (GIST). PD-L1 in macrophages and
lymphocytes has been detected in 30 and 58 % of the
cases, respectively. In this study, it has not been found an
association between PD-L1 expression and clinical features
and also overall survival, probably due to heterogenous
patient population as in our study group [18]. We had no
GIST in our study group. We did not make survival anal-
ysis according to the PD-1/PD-L1 expression due to the
heterogenous population and limited number of the cases in
each subgroup of sarcomas.
In osteosarcoma cell lines and tissue samples taken from
patients with osteosarcoma, PD-L1 has been explored by real
timeRT-PCR. It has been found very high levels of PD-L1, and
PD-L1 has been found to be associated with tumor infiltrating
lymphocytes [19]. PD-1 expression in 56 cases with osteosar-
coma has been measured by flow cytometry on peripheral
CD4? and CD8? T cells and has been compared with 42
healthy controls. PD-1 has been found to be significantly higher
in osteosarcomapatients, andhigher levels of PD-1onCD4?T
cells have been found in metastatic cases and cases with frac-
ture. It has been suggested by authors that PD-1 is involved in
the pathogenesis of osteosarcoma, especially in the progression
of disease [20]. In our study, PD-1 was detected in 2 cases and
PD-L1 in 3 cases in tumor tissues, and we did not detect
expression inmicroenvironment. This discrepancymay be due
to methodologic differences. Of course, RT-PCR is more sen-
sitive compared with immunohistochemistry.
Kaposi sarcoma is an interesting subtype of sarcoma
suggesting the important role of immune system in tumor
elimination. Responsible virus is human herpesvirus-8, and
Kaposi sarcoma is generally seen in untreated HIV cases
[21]. Resolution of Kaposi sarcoma lesions after successful
anti-retroviral therapy suggests the role of immune system
in Kaposi sarcoma [22]. In our study, 4 of 5 cases with
Kaposi sarcoma showed PD-1 or PD-L1 expression. This
finding is important. Because there is no definitive treat-
ment for these cases, checkpoint blocking treatment tar-
geting PD-1 pathway may be useful in this entity.
In addition to the sarcoma samples, PD-L1 and/or PD-
L2 have been studied in cancer patients with sarcomatoid
component. In 2 studies covering 41 cases with pleo-
morphic cancer and 13 sarcomatoid carcinomas of the
lung, expression has been found in 70–90 % of the cases.
Interestingly, more PD-L1 expression has been found in
sarcomatous component compared with carcinomatous
areas [23, 24]. It has been suggested that PD-1/PD-L1 is
important biomarkers for prognosis and also possible
targets for treatment [8, 24]. These results suggest the role
of programmed death pathway in sarcomas and also tar-
geting this pathway in tumors with mesenchymal
component.
An interesting point of our study was the strongest
expression of PD-1/PD-L1 expression in cases with the
history of previous giant cell bone tumor. This finding need
to be validated in cases with giant cell bone tumor and also
their transformed forms.
It is very well known that evaluating PD-L1 expression
at an isolated time point may not represent its true preva-
lence. Limitations of our study were the heterogeneity of
the samples and also limited number of each histological
subtype, so we could not make a reasonable comment
about the PD-1/PD-L1 expression in sarcomas. It is known
that expression of PD-1/PD-L1 expressions is a dynamic
process and is affected by chemotherapy and/or radiation
which are commonly used in sarcoma cases. Perhaps
repeated PD-1/PD-L1 analyses will be more informative to
Table 5 Clinicopathologic variables, treatment details and PD-1/PD-L1 expression in Kaposi sarcoma
Pt no Histopathologic
subtype
Age
Sex
Localization Treatment Metastasis
site
PD-1
tumor
PD-1
ME
PD-L1
tumor
PD-L1
ME
PFS OS
1 Kaposi sarcoma 58 M Finger ABV Skin – – ? ? 116?
2 Kaposi sarcoma 75 M Hand – – – –
3 Kaposi sarcoma 50 F Skin Lypos doxorubicin
thalidomide
– ? ? ? 15 59
4 Kaposi sarcoma 68 M Skin Lypos doxorubicin
vinblastine
– – ? (focal) ? (focal) 106?
5 Kaposi sarcoma 65 F Skin Lypos doxorubicin
vinblastine
– – ? (focal) ? (focal) 101?
M male, F female, LG low grade, IG intermediate grade, HG high grade, ME microenvironment, PFS progression free survival, OS overall
survival
93 Page 6 of 10 Med Oncol (2016) 33:93
123
Table
6Clinicopathologic
variables,treatm
entdetails
andPD-1/PD-L1expressionin
synovialsarcoma
Pt
no
Histopathologic
subtype
Age
Sex
Localization
Tumor
diameter
Margin
Treatment
Metastasis
site
PD-1
tumor
PD-1
ME
PD-L1
tumor
PD-L1
ME
PFS
OS
1Synovialsarcoma
biphasic
23M
Inguinal
mass
?–
?–
2Synovialsarcoma
monophasic
50M
Fem
oral
region
89
6.5
97.5
––
––
16?
3Synovialsarcoma
47F
Fem
oral
region
14X9
MAID
Gem
–doce
temozolomide
Lung
––
––
–20
4Synovialsarcoma
biphasic
51F
Calcaneus
79
79
3Negative
MAID
––
––
–14?
14?
Mmale,
Ffemale,
LG
low
grade,
IGinterm
ediate
grade,
HG
highgrade,
MEmicroenvironment,PFSprogressionfree
survival,OSoverallsurvival
Table
7Clinicopathologic
variables,treatm
entdetails
andPD-1/PD-L1expressionin
pleomorphic
sarcoma
Pt
no
Histopathologic
subtype
Grade
Age
Sex
Localization
Tumor
diameter
Margin
Treatment
Metastasis
site
PD-1
tumor
PD-1
ME
PD-L1
tumor
PD-L1
ME
PFS
OS
1Pleomorphic
sarcoma
(Previousgiantcelltumor*)
40M
Fem
ur
89
79
6Repeated
curettages
??
????
?
2Pleomorphic
sarcoma
HG
55M
Fem
oral
region
59
5Negative
MAID
Gem
–doce
Lung,skin,
bone
––
––
14
25
3Pleomorphic
sarcoma
HG
30M
Tibia
299
199
15
Negative
IFODOX
Gem
–doce
temozolomide
pazopanib
Lung
––
??
430
4Pleomorphic
sarcoma
HG
42F
Fem
oris
muscle
99
3Negative
MAID
Gem
–doce
pazopanib
Lung
––
––
15
21
5Pleomorphic
sarcoma
HG
60M
Fem
ur
59
49
4Positive
MAID
Gem
–doce
Lung
––
––
19
20?
6Pleomorphic
sarcoma
HG
49M
Axillary
region
89
7.5
97.5
Negative
––
–?
?26?
26?
Mmale,
Ffemale,
LG
low
grade,
IGinterm
ediate
grade,
HG
highgrade,
MEmicroenvironment,PFSprogressionfree
survival,OSoverallsurvival
Med Oncol (2016) 33:93 Page 7 of 10 93
123
Table
8Clinicopathologic
variables,treatm
entdetails
andPD-1/PD-L1expressionin
other
sarcomasubtypes
Pt
no
Histopathologic
subtype
Grade
Age
Sex
Localization
Tumordiameter
Margin
Treatment
Metastasis
site
PD-1
tumor
PD-1
ME
PD-L1
tumor
PD-L1
ME
PFS
OS
1Fibrosarcoma
HG
29F
Fem
oralregion
209
179
13
Positive
MAID
Gem
–doce
Retroperitoneum
?–
–?
17
234?
2Fibrosarcoma
HG
29M
Fem
oralregion
Negative
MAID
Gem
–doce
Iliacmass
––
–?
(focal)
16
40
3Fibrosarcoma(Previousgiant
celltumor)
HG
46M
(21)
Lung(Fem
ur)
Disseminated
lung
metastases
Repeated
curettages
MAID
Gem
–doce
Lung
??
??
?250
310
4STUMPMETASTASIS
LG
36F
UterusLung
metastasis
69
3.5
92
Negative
MAID
Lung
––
–?
62
98?
5Clear
cellsarcoma
24F
Cruris
7.5
969
8Negative
MAID
––
––
6Inflam
matory
myofibroblastic
tumor
43F
Ovaries
69
59
3
59
49
4
Metastatic
disease
–Ovariesliver
?(poor)
–?
(poor)
–16?
7Epithelioid
sarcoma
30M
Fem
ur
69
59
4Negative
––
–?
8Dedifferentiated
chondrosarcoma
HG
60F
Gluteusmuscle
79
79
7Nosurgery
Doxorubicin
Cisplatinum
––
––
11?
9Indifferentiated
sarcoma
17F
Uterus
149
139
3Negative
––
–?
–
10
Indifferentiated
sarcoma
43F
Pelvic
mass
59
39
2MAID
––
––
?27
11
Unclassified
sarcoma
52M
Maxillary
sinus
89
79
2Positive
MAID
––
–?
?13?
13?
12
Unclassified
sarcoma
66M
Thoraxwall
Nosurgery
MAID
Lung
––
––
12?
12?
13
Malignantfibroushistiocytoma
40F
Fem
ur
49
2Negative
MAID
––
––
–18?
18?
14
Malignantfibroushistiocytoma
48F
Sphenoid
sinus
49
3Positive
MAID
Gem
–doce
pazopanib
Local
––
??
12
36?
Mmale,
Ffemale,
LG
low
grade,
IGinterm
ediate
grade,
HG
highgrade,
MEmicroenvironment,PFSprogressionfree
survival,OSoverallsurvival,STUMPsm
ooth
muscle
tumorunknown
metastasispotential
93 Page 8 of 10 Med Oncol (2016) 33:93
123
determine the role of PD-1 pathway in the biology and
management of sarcomas.
In conclusion, programmed death pathway is involved in
sarcoma development/biology and larger studies will be
more informative for targeted treatment and/or checkpoint
blocking therapies. Results of the open-label single-arm
phase II study (SARC028) using pembrolizumab will be
important for the detection of efficacy of checkpoint
blocker treatment in sarcomas.
Acknowledgments This study has been supported by Cukurova
University Research Fund.
Compliance with ethical standards
Conflict of interest None.
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