CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome
Aim: To evaluate the association between the presence of CD8 and CD45RO T lymphocytes in bone marrow (BM), disseminated tumor cells (DTCs), tumor hypoxia and their impact on disease outcome. Material and methods: 91 naïve gastric cancer (GC) patients were enrolled into the study. DTCs, CD8- and CD45...
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| Date: | 2015 |
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Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2015
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| Cite this: | CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome / S. Osinsky, A. Kovelskaya, L. Bubnovskaya, D. Osinsky, S. Merentsev // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 48-52. — Бібліогр.: 27 назв. — англ. |
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Digital Library of Periodicals of National Academy of Sciences of Ukraine| _version_ | 1860244167136903168 |
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| author | Osinsky, S. Kovelskaya, A. Bubnovskaya, L. Osinsky, D. Merentsev, S. |
| author_facet | Osinsky, S. Kovelskaya, A. Bubnovskaya, L. Osinsky, D. Merentsev, S. |
| citation_txt | CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome / S. Osinsky, A. Kovelskaya, L. Bubnovskaya, D. Osinsky, S. Merentsev // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 48-52. — Бібліогр.: 27 назв. — англ. |
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| container_title | Experimental Oncology |
| description | Aim: To evaluate the association between the presence of CD8 and CD45RO T lymphocytes in bone marrow (BM), disseminated tumor cells (DTCs), tumor hypoxia and their impact on disease outcome. Material and methods: 91 naïve gastric cancer (GC) patients were enrolled into the study. DTCs, CD8- and CD45RO-positive T lymphocytes in BM were detected using immunocytochemistry. All patients were thoroughly informed about the study that was approved by the local ethics committee. Statistical analyses were done using NCSS2000/PASS2000 and Prism, version 4.03 software packages. Results: It was detected that 80.5 and 81.3% of patients had CD8- and CD45RO-positive T cells in BM, respectively. When DTCs were detected in BM, the number of patients with CD8-and CD45RO-positive T cells in BM were 86.1 and 84.4%, respectively. It was also determined that the number of patients with DTCs in BM with categories M0 and M1 and with CD8- and CD45RO-positive T cells in BM were 86.2 and 85.7%, 85.7 and 80.0%, respectively. The association between DTCs in BM and presence of CD8 and CD45RO T cells lymphocytes in BM was not found. At the same time it was shown the association between presence of CD8 and CD45RO T lymphocytes and survival. The presence of CD8- and CD45RO-positive T cells in BM were accompanied with significantly longer overall survival of patients compared to that of patients without CD8- and CD45RO-positive T cells in BM. Conclusion: Patients with the presence of CD8- and CD45RO-positive T cells in BM demonstrated better survival of GC patients than those with the absence of these cells in BM. It may be suggested that tumor cells in BM are controlled in a dormant state by T cells in BM, in particular by CD8-positive T cells. Key Words: CD8 T lymphocytes, CD45RO T lymphocytes, bone marrow, disseminated tumor cells, tumor hypoxia, survival.
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48 Experimental Oncology 37, 48–52, 2015 (March)
CD8 AND CD45RO T LYMPHOCYTES IN BONE MARROW
OF GASTRIC CANCER PATIENTS: CORRELATION
WITH DISSEMINATED TUMOR CELLS AND DISEASE OUTCOME
S. Osinsky1*, A. Kovelskaya1, L. Bubnovskaya1, D. Osinsky2, S. Merentsev2
1R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine, Kyiv 03022, Ukraine
2Kyiv City Clinical Oncological Center, Kyiv 03115, Ukraine
Aim: To evaluate the association between the presence of CD8 and CD45RO T lymphocytes in bone marrow (BM), disseminated
tumor cells (DTCs), tumor hypoxia and their impact on disease outcome. Material and methods: 91 naïve gastric cancer (GC) patients
were enrolled into the study. DTCs, CD8- and CD45RO-positive T lymphocytes in BM were detected using immunocytochemistry.
All patients were thoroughly informed about the study that was approved by the local ethics committee. Statistical analyses were done
using NCSS2000/PASS2000 and Prism, version 4.03 software packages. Results: It was detected that 80.5 and 81.3% of patients
had CD8- and CD45RO-positive T cells in BM, respectively. When DTCs were detected in BM, the number of patients with CD8-and
CD45RO-positive T cells in BM were 86.1 and 84.4%, respectively. It was also determined that the number of patients with DTCs
in BM with categories M0 and M1 and with CD8- and CD45RO-positive T cells in BM were 86.2 and 85.7%, 85.7 and 80.0%, re-
spectively. The association between DTCs in BM and presence of CD8 and CD45RO T cells lymphocytes in BM was not found.
At the same time it was shown the association between presence of CD8 and CD45RO T lymphocytes and survival. The presence
of CD8- and CD45RO-positive T cells in BM were accompanied with significantly longer overall survival of patients compared to that
of patients without CD8- and CD45RO-positive T cells in BM. Conclusion: Patients with the presence of CD8- and CD45RO-posi-
tive T cells in BM demonstrated better survival of GC patients than those with the absence of these cells in BM. It may be suggested
that tumor cells in BM are controlled in a dormant state by T cells in BM, in particular by CD8-positive T cells.
Key Words: CD8 T lymphocytes, CD45RO T lymphocytes, bone marrow, disseminated tumor cells, tumor hypoxia, survival.
It is known that tumor cells may be found in the bone
marrow (BM) of patients with a variety of malignant tu-
mors categorized as M0 category [1–3]. The tumor cells
in BM were named disseminated tumor cells (DTCs) [4].
It was shown that persistence of DTCs in BM is an in-
dependent prognostic factor for unfavorable disease
outcome [2, 5, 6]. Moreover, there are data that DTCs
may persist in the organism within long time without
manifestation of disease [5, 7–10]. Such state is known
as tumor dormancy that is very intensively studied
in many laboratories and clinics [10–14]. Interestingly,
that it was suggested some years ago that BM and lymph
nodes are privileged sites where tumor cells are con-
trolled in a dormant state by the immune system [15].
Shen et al. [16] mentioned about interesting observation
that DTCs derived from a variety of epithelial tumors seem
to have a propensity to home to BM, including tumors
which do not commonly form bone metastasis, such
as colon cancer. This implies that BM might be a reservoir
for DTCs from where they may recirculate into circulating
system and then colonize in other distant organs. It has
been shown that DTCs resist to chemotherapy and hor-
monal therapy, and survive in BM for years to decades.
DTCs are dormant. Dormancy is related to cytostatic drug
resistance and may be a pro perty of minimal residual
disease and tumor stem cells.
One of the main problems is a question about
mechanisms that can control the long-term persistence
of DTCs in BM before the relapse or metastasis. The an-
swer on this question could help to develop the methods
to control the tumor dormancy, predict relapse of dise-
ase and propose the adequate therapy. In this context
there are very important data about the participation
of memory T cells occupied BM in the control of tumor
dormancy. Farrar et al. [17] have used the murine B cell
lymphoma (BCL1) as a model of tumor dormancy in mice
vaccinated with the BCP1 Ig and demonstrated that
CD8-positive, but not CD4-positive, T cells are required
for the maintenance of dormancy in BCL1 Ig-immunized
BALB/c. Authors suggested that CD8-positive T cells
via endo genous production of IFN-γ in collaboration
with humoral immunity can induce and maintain the
tumor dormancy. Feuerer et al. [18] have shown that
breast cancer patients with DTCs in their BM had
more memory CD4 T cells and more CD56+CD8+ cells
than patients with tumor cell-negative BM. Taking
into account obtained results authors hypothesized
that “BM is a special compartment for immunological
memory and tumor dormancy”. Later these authors
have shown that BM and tumors of transgenic mice
contain high number of CD8-positive T cells specific for
the melanoma antigen tyrosinase-related protein and
showing mostly effector memory phenotype [19]. It was
suggested that thereby memory T cells could control
disseminated melanoma cells. Mahnke et al. [20] have
suggested that the BM microenvironment has special
features for the maintenance of tumor dormancy and
immunological T-cell memory. Recent publications
presented the data confirming this suggestion [21, 22].
It has to be noted that the publications aimed to find
the association between DTCs and memory T cells
Submitted: November 04, 2014.
*Correspondence: E-mail: osion@onconet.kiev.ua
Abbreviations used: BCL1 — B cell lymphoma; BM — bone marrow;
DTCs — disseminated tumor cells; GC — gastric cancer; OS —
overall survival.
Exp Oncol 2015
37, 1, 48–52
Experimental Oncology 37, 48–52, 2015 (March) 49
in BM are limited especially in the clinical setting. Many
questions are left to be received the answers to clarify
the control of tumor dormancy by host immune reac-
tions. Pantel et al. [1] concluded that the role of the
immune system in dormancy control and metastatic
progression has not been proved.
In gastric cancer (GC) patients DTCs were also
found [23]. Our previous study has shown that DTCs
were detected in 51.4% of GC patients with M0, and
overall survival (OS) of patients with M0 and DTCs was
shorter than that of patients without DTCs (patients
in both groups were operated only) (p = 0.0497) [24].
Taking into account these data and the virtual absence
of the data concerning association between memory
T cells in BM and DTCs we have aimed to find the pos-
sible association between presence both of DTCs and
CD8- and CD45RO-positive T cells in BM and evaluate
the correlation between CD8- and CD45RO-positive
T cells in BM and clinical outcome.
МАTERIALS AND METHODS
Patients. A total of 91 patients (61 men and 30 wo-
men) with primary GC were diagnosed and treated
at the City Clinical Oncological Center (Kyiv), during
period 2008–2011. No patient received chemotherapy
or radiation prior to surgery, and the majority of patients
with advanced cancer had received adjuvant chemo-
therapy. Tissue samples were taken immediately after
tumor excision. Tumors were classified and staged
according to the 2002 version of the UICC staging
system [25]. Histological types of tumor were evalu-
ated by WHO histological classification (2000) [26]. All
patients were thoroughly informed about the study that
was approved by the local ethics committee.
Detection of tumor cells, CD8- and CD45RO-posi-
tive T cells in BM. Preoperatively, 2.0–3.0 mL of BM aspi-
rates from the sternum with conventional cautions to avoid
the hit of skin epithelial cells into the sample was taken
into a heparinized syringe and transferred into a tube
“Sarstedt” containing EDTA. After ficoll-hypaque den-
sity centrifugation (density, 1.077; Sigma-Aldrich, USA)
to isolate the mononuclear cell fraction (1105 g for 20 min),
the interphase was washed twice in phosphate-buffered
saline (PBS) with removing of erythrocytes (Uti-Lyse
Erythrocyte Lysing Reagent, Dako Cytomation, USA),
resuspended to a concentration of 570•103 cells/30 μL,
and cytocentrifuged on glass slides. Specimens were air-
dried from 12 to 24 hs and stained immediately or stored
at –20 °C. Detection of tumor cells (cytokeratin-positive
cells) in BM cytospins was performed as presented in [24].
For the detection of CD8 and CD45RO T cells
in BM cytospin preparations were fixed by formol-ace-
tone solution (pH 6.6) in accordance with the instruc-
tion. Slides were treated by 0.3% Triton X-100 solution,
washed by PBS and blocking of endogenous peroxi-
dase followed by incubation in 3% bovine serum albu-
min to switch off nonspecific reaction antigen-antibody.
Cytospins were incubated with primary monoclonal
mouse antibodies against CD8 (clone C8/144B, ready-
to-use, Dako, Denmark) or with primary monoclonal
mouse antibodies against CD45RO (clone UCHL1,
Sigma, США) in optimal dilution (1:400) within 1 h. After
washing of primary antibodies slides were processed
with PolyVueHRP Detection System Components
(Diagnostic BioSystems, USA). Visualization of peroxi-
dase activity was provided by staining with DAB (Dako,
Denmark). Cytospins were counterstained by solution
of Methyl Green (ready-to-use, Dako, Denmark) within
1–2 min. Cytospins were examined by light microscopy
(×1000) to detect CD8- and CD45RO-positive T cells.
Tumor hypoxia evaluation by 31P NMR spectros-
copy. Level of tumor hypoxia was assessed with 31P
NMR spectroscopy. 31P NMR spectra of perchloric acid
(PCA) tumor extracts were acquired by means of a high-
resolution Bruker 400 MHz spectrometer (Widebore
Ultrashield, AV-400 electronics, Germany) using a probe
of 5 mm inner diameter. All details of method were pre-
sented in our earlier publication [27].
Statistical analysis. All statistical analyses were
conducted using the NCSS 2000/PASS 2000 and
Prism, version 4.03, software packages. Correlations
were analyzed with the Pearson correlation coefficient.
The χ2 test was performed to determine the correla-
tion between the CD8 and CD45RO status of BM and
the clinicopathological characteristics. The survival
proportion was estimated by using the Kaplan — Meier
method and differences in survival were analyzed with
the log-rank test. Prognostic values of relevant variables
were analyzed by means of the Cox proportional ha-
zards model using hazard ratio and χ2 test. Two-tailed
p values <0.05 were considered statistically significant.
RESULTS AND DISCUSSION
CD8- and CD45RO-positive cells in BM and their
correlation with clinical variables. Individual patient
data from a total 91 histological confirmed GC patients
were included in this study (Table 1). The median age was
62 years. Overall, 80.5 and 81.3% of patients had CD8-
and CD45RO-positive T lymphocytes in BM, respectively.
There was no association between presence of CD8-
or CD45RO-positive T cells in BM and clinicopathological
characteristics (Tables 2 and 3). A marked predominance
of the number of patients characterized by the presence
of CD8- and CD45RO-positive T cells in BM with M0 cat-
egory on patients with CD8- and CD45RO-positive T cells
in BM but with M1 category was not statistically significant.
CD8- and CD45RO-positive cells and DTCs
in BM. When DTCs were detected in BM the number
of patients with BM that was positive to CD8 and
CD45RO T cells were 86.1 and 84.4%, respectively.
It was also determined that the number of patients with
DTCs in BM with categories M0 and M1 and with CD8-
and CD45RO-positive T cells in BM was 86.2; 85.7;
85.7 and 80.0%, respectively. It is clearly seen that the-
re is not association between DTCs in BM and pre sence
of CD8 and CD45RO T cells lymphocytes in BM. It may
be suggested that entering the tumor cells into BM is not
linked with the presence and acti vity of CD8 and CD45RO
T cells in BM, but most likely CD8 and CD45RO T cells
determine the subsequent behavior of DTCs.
50 Experimental Oncology 37, 48–52, 2015 (March)
Table 1. Patient and tumor characteristics
Characteristics Number, 91 (%)
Gender
Male 61 (67.0)
Female 30 (33.0)
Age (years)
Median 62
Range 26–84
Tumor location
Upper third 11 (12.1)
Middle third 20 (22.0)
Lower third 53 (58.2)
Total 7 (7.7)
UICC stage
I 18 (19.8)
II 16 (17.6)
III 28 (30.7)
IV 29 (31.9)
Histological type
Adenocarcinoma 65 (71.4)
Mucinous adenocarcinoma 11 (12.1)
Signet-ring cell carcinoma 12 (13.2)
Undifferentiated carcinoma 3 (3.3)
Grade (G)
1 5 (5.5)
2 19 (20.9)
3 60 (65.9)
4 7 (7.7)
T-classification
T1 9 (9.9)
T2 13 (14.3)
T3 36 (39.5)
T4 33 (36.3)
Nodal involvement
N0 44 (48.4)
N1–2 47 (51.6)
Distant metastasis
M0 75 (82.4)
M1 16 (17.6)
Table 2. Prevalence of CD8+ T cells in BM of GC patients by clinical variables
Variables
Patients with CD8+ T cells in BM
ppresent
(n = 62, 80.5%)
absent
(n = 15, 19.5%)
Gender
Male 39 (62.9) 10 (66.7)
Female 23 (37.1) 5 (33.3)
Age (years)
Median (range) 60.5 (26–84) 64.0 (29–79)
Tumor location
Upper third 5 (8.1) 1 (6.7) 0.1297
Middle third 16 (25.8) 1 (6.7)
Lower third 38 (61.3) 10 (66.6)
Total 3 (4.8) 3 (20.0)
UICC stage
I 9 (14.5) 4 (26.7) 0.5253
II 12 (19.4) 4 (26.7)
III 20 (32.3) 4 (26.7)
IV 21 (33.8) 3 (20.0)
Histological type
Adenocarcinoma 46 (74.2) 11 (73.4) 0.8192
Mucinous adenocarcinoma 6 (9.7) 2 (13.3)
Signet-ring cell carcinoma 7 (11.3) 2 (13.3)
Undifferentiated carcinoma 3 (4.8) 0
Grade (G)
1 3 (4.8) 1 (6.7) 0.3686
2 10 (16.1) 5 (33.3)
3 45 (72.6) 9 (60.0)
4 4 (6.5) 0
T-classification
T1 5 (8.1) 3 (20.0) 0.1648
T2 5 (8.1) 2 (13.3)
T3 26 (41.9) 8 (53.4)
T4 26 (41.9) 2 (13.3)
Nodal involvement
N0 30 (48.4) 7 (46.7) 0.9097
N1–2 32 (51.6) 8 (53.3)
Distant metastasis
M0 52 (83.9) 13 (86.7) 0.7887
M1 10 (16.1) 2 (53.3)
CD8- and CD45RO-positive cells in BM and hy-
poxia level in primary tumor. Level of tumor hypoxia
assessed by NMR spectroscopy was ranged as fol-
lows: if the PME/Pi < 1.0, tumors are characte rized
by severe hypoxia, 1.0 < PME/Pi < 1.4 moderate
hypoxia, 1.4 < PME/Pi < 2.0 mild hypoxia, and PME/
Pi > 2.0 weak hypoxia (satisfactory oxygenation).
The association between presence of CD8- and
CD45RO-positive T cells in BM and hypoxia level
in tumor was not detected: CD8-positive T cells were
found in 81.8% of patients with tumors characterized
by severe and moderate hypoxia and 84.2% of patients
with tumor characte rized by mild and weak hypoxia,
and CD45RO-positive T cells in 86.7 and 82.6%, re-
spectively. Obtained results have shown that tumor
hypoxia do not associate with the presence of CD8 and
CD45RO T cells in BM and, probably, do not influence
their activity.
Table 3. Prevalence of CD45RO+ T cells in BM of GC patients by clinical
variables
Variables
Patients with CD45RO+ T cells
in BM ppresent
(n = 74, 81.3%)
absent
(n = 17, 18.7%)
Gender
Male 49 (66.2) 12 (70.6)
Female 25 (33.8) 5 (29.4)
Age (years)
Median (Range) 61 (26–84) 64 (29–81)
Tumor location
Upper third 10 (13.5) 1 (5.9) 0.4477
Middle third 18 (24.3) 2 (11.8)
Lower third 41 (55.4) 12 (70.5)
Total 5 (6.8) 2 (11.8)
UICC stage
I 15 (20.3) 3 (17.7) 0.4540
II 12 (16.2) 4 (23.5)
III 24 (32.4) 4 (23.5)
IV 23 (31.1) 6 (35.3)
Histological type
Adenocarcinoma 51 (68.9) 14 (82.3) 0.5153
Mucinous adenocarcinoma 10 (13.5) 1 (5.9)
Signet-ring cell carcinoma 11 (14.9) 1 (5.9)
Undifferentiated carcinoma 2 (2.7) 1 (5.9)
Grade (G)
1 4 (5.4) 1 (5.9) 0.3617
2 15 (20.3) 4 (23.5)
3 49 (66.2) 11 (64.7)
4 23 (31.1) 1 (5.9)
T-classification
T1 6 (8.1) 3 (17.6) 0.6900
T2 11 (14.9) 2 (11.8)
T3 30 (40.5) 6 (35.3)
T4 27 (36.5) 6 (35.3)
Nodal involvement
N0 35 (47.3) 9 (52.9) 0.6745
N1–2 39 (52.7) 8 (47.1)
Distant metastasis
M0 62 (83.8) 13 (76.5) 0.4750
M1 12 (16.2) 4 (23.5)
OS of patients with CD8- and CD45RO-positive
cells in BM. OS was significantly longer in patients
with tumors characterized by the presence of CD8- and
CD45RO-positive T cells in BM as compared to pa-
tients with the absence of CD8- and CD45RO-positive
T cells in BM (log-rank test: p = 0.0343 and p = 0.0235,
respectively, Fig. 1 and 2). It was also determined that
OS in patients with DTCs in BM and with presence
of CD8-positive T cells in BM was significantly longer
in compared with that in patients with DTCs in BM and
without CD8-positive T cells in BM (log rank test:
p = 0.0226, Fig. 3).
Experimental Oncology 37, 48–52, 2015 (March) 51
0
0
20
40
60
80
100
50 7525 100
Weeks
Su
rv
iva
l,
%
150125 175
Fig. 1. Kaplan — Meier OS curves for GC patients as a function
of CD8+ presence in BM (presence of CD8+ T cells in BM, thin
line; absence of CD8+ in BM, bold line p = 0.0343). All patients
were analyzed
0
0
20
40
60
80
100
50 100
Weeks
Su
rv
iva
l,
%
150 200 250
Fig. 2. Kaplan — Meier OS curves for GC patients as a func-
tion of CD45RO+ T cells in BM (presence of CD45RO+ T cells
in BM, thin line; absence of CD45RO+ T cells in BM, bold line,
p = 0.0235). All patients were analyzed
0
0
20
40
60
80
100
50 7525 100
Weeks
Su
rv
iva
l,
%
150125 175
Fig. 3. Kaplan — Meier OS curves for GC patients as a function
of CD8+ presence in BM (presence of CD8+ T cells in BM, thin
line; absence of CD8+ in BM, bold line p = 0.0226). All patients
with DTCs in BM were analyzed
The same association was found for CD45RO-
positive T cells, but it was not statistically significant
(log-rank test: p = 0.0537, Fig. 4). OS in patients with
M0 category was also longer in patients with the pre-
sence of CD8- and CD45RO-positive T cells in BM, but
this link was not statistically significant (log-rank test:
p = 0.0538, Fig. 5 and p = 0.0862, Fig. 6, respectively).
Separate analysis of OS in patients with M0 catego-
ry having DTCs in BM demonstrated that association
between the presence of CD8- and CD45RO-positive
T cells in BM and OS was also existed but it was not
statistically significant (log-rank rest: p = 0.0674 and
p = 0.9054, respectively, figures were not presented).
It has to be noted that the association between
the presence of CD8- and CD45RO-positive T cells
in BM and OS in patients who have been treated with
operation alone or adjuvant chemotherapy was not sta-
tistically significant. It was found only the tendency for
the association between the pre sence of CD8-positive
T cells in BM and OS in patients treated with opera-
tion alone or with adjuvant chemotherapy (log-rank
test: p = 0.0529 and p = 0.0529, respectively, figures
were not presented). Obtained results have shown
the association between the presence of CD8- and
CD45RO-positive T cells in BM and OS of patients,
in particular OS was statistically longer in all patients
with CD8- and CD45RO-positive T cells in BM than
that in patients with CD8- and CD45RO-negative
BM. It is very important to note that OS in patients with
DTCs in BM and with CD8-positive T cells in BM was
significantly longer than that in patients with CD8-
negative BM (p = 0.0226).
Median follow-up time was 16.0 (range 0.36–54.4)
months from diagnosis for all patients. Overall,
31 patients (34.1%) died during follow-up. In 29 pa-
tients (93.5%) death was related to GC. Of these,
78.3% of patients had CD8- and 96.6% of patients
had CD45RO-positive T cells in BM. Survival time
for patients with the presence of CD8- or CD45RO-
positive T cells in BM was 19.6 ± 1.9 months and
20.4 ± 1.5 months, respectively.
0
0
20
40
60
80
100
50 100
Weeks
Su
rv
iva
l,
%
150 200 250
Fig. 4. Kaplan — Meier OS curves for GC patients as a func-
tion of CD45RO+ T cells in BM (presence of CD45RO+ T cells
in BM, thin line; absence of CD45RO+ T cells in BM, bold line,
p = 0.0537). All patients with DTCs in BM were analyzed
0
0
20
40
60
80
100
50 7525 100
Weeks
Su
rv
iva
l,
%
150125 175
Fig. 5. Kaplan — Meier OS curves for GC cancer patients
as a function of CD8+ presence in BM (presence of CD8+ T cells
in BM, thin line; absence of CD8+ in BM, bold line p = 0.0538).
All patients with M0 category were analyzed
52 Experimental Oncology 37, 48–52, 2015 (March)
0
0
20
40
60
80
100
50 100
Weeks
Su
rv
iva
l,
%
150 200 250
Fig. 6. Kaplan — Meier OS curves for GC patients as a func-
tion of CD45RO+ T cells in BM (presence of CD45RO+ T cells
in BM, thin line; absence of CD45RO+ T cells in BM, bold line,
p = 0.0862). All patients with M0 category were analyzed
In conclusion, it may summarized that 80.5%
of GC patients had CD8-positive T cells and 81.3% had
CD45RO-positive T cells in BM. 86.1% of patients with
CD8-positive T cells in BM and 84.4% of patients with
CD45RO-positive T cells had DTC in BM. GC patients
with the presence of CD8- and CD45RO-positive
T cells in BM demonstrated better OS than those with
the absence of CD8- and CD45RO-positive T cells
in BM. The results of our investigations and literature
data allow to suggest that tumor cells in BM may be exi-
sted in a dormant state through the control by T cells,
in particular by CD8-positive T cells.
ACKNOWLEDGEMENT
This research was supported by the National Aca-
demy of Sciences of Ukraine (Grants no. 0102U003228).
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Copyright © Experimental Oncology, 2015
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| id | nasplib_isofts_kiev_ua-123456789-145455 |
| institution | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| issn | 1812-9269 |
| language | English |
| last_indexed | 2025-12-07T18:34:31Z |
| publishDate | 2015 |
| publisher | Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| record_format | dspace |
| spelling | Osinsky, S. Kovelskaya, A. Bubnovskaya, L. Osinsky, D. Merentsev, S. 2019-01-21T21:27:43Z 2019-01-21T21:27:43Z 2015 CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome / S. Osinsky, A. Kovelskaya, L. Bubnovskaya, D. Osinsky, S. Merentsev // Experimental Oncology. — 2015. — Т. 37, № 1. — С. 48-52. — Бібліогр.: 27 назв. — англ. 1812-9269 https://nasplib.isofts.kiev.ua/handle/123456789/145455 Aim: To evaluate the association between the presence of CD8 and CD45RO T lymphocytes in bone marrow (BM), disseminated tumor cells (DTCs), tumor hypoxia and their impact on disease outcome. Material and methods: 91 naïve gastric cancer (GC) patients were enrolled into the study. DTCs, CD8- and CD45RO-positive T lymphocytes in BM were detected using immunocytochemistry. All patients were thoroughly informed about the study that was approved by the local ethics committee. Statistical analyses were done using NCSS2000/PASS2000 and Prism, version 4.03 software packages. Results: It was detected that 80.5 and 81.3% of patients had CD8- and CD45RO-positive T cells in BM, respectively. When DTCs were detected in BM, the number of patients with CD8-and CD45RO-positive T cells in BM were 86.1 and 84.4%, respectively. It was also determined that the number of patients with DTCs in BM with categories M0 and M1 and with CD8- and CD45RO-positive T cells in BM were 86.2 and 85.7%, 85.7 and 80.0%, respectively. The association between DTCs in BM and presence of CD8 and CD45RO T cells lymphocytes in BM was not found. At the same time it was shown the association between presence of CD8 and CD45RO T lymphocytes and survival. The presence of CD8- and CD45RO-positive T cells in BM were accompanied with significantly longer overall survival of patients compared to that of patients without CD8- and CD45RO-positive T cells in BM. Conclusion: Patients with the presence of CD8- and CD45RO-positive T cells in BM demonstrated better survival of GC patients than those with the absence of these cells in BM. It may be suggested that tumor cells in BM are controlled in a dormant state by T cells in BM, in particular by CD8-positive T cells. Key Words: CD8 T lymphocytes, CD45RO T lymphocytes, bone marrow, disseminated tumor cells, tumor hypoxia, survival. This research was supported by the National Academy of Sciences of Ukraine (Grants no. 0102U003228). en Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України Experimental Oncology Original contributions CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome Article published earlier |
| spellingShingle | CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome Osinsky, S. Kovelskaya, A. Bubnovskaya, L. Osinsky, D. Merentsev, S. Original contributions |
| title | CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome |
| title_full | CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome |
| title_fullStr | CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome |
| title_full_unstemmed | CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome |
| title_short | CD8 and CD45RO T lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome |
| title_sort | cd8 and cd45ro t lymphocytes in bone marrow of gastric cancer patients: correlation with disseminated tumor cells and disease outcome |
| topic | Original contributions |
| topic_facet | Original contributions |
| url | https://nasplib.isofts.kiev.ua/handle/123456789/145455 |
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