Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer
Cancer, inflammation and immune surveillance recruit lymphocytes as common key cellular players. The aim of the study was to assess a utility of the absolute and relative lymphocyte counts (ALC and RLC) in peripheral blood of patients with urological cancer as sensitive tool in pretreatment assessme...
Gespeichert in:
| Datum: | 2018 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | English |
| Veröffentlicht: |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
2018
|
| Schriftenreihe: | Experimental Oncology |
| Schlagworte: | |
| Online Zugang: | http://dspace.nbuv.gov.ua/handle/123456789/145567 |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| Назва журналу: | Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| Zitieren: | Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer / P. Yakovlev, D. Klyushin // Experimental Oncology. — 2018 — Т. 40, № 2. — С. 119–123 — Бібліогр.: 17 назв. — англ. |
Institution
Digital Library of Periodicals of National Academy of Sciences of Ukraine| id |
irk-123456789-145567 |
|---|---|
| record_format |
dspace |
| spelling |
irk-123456789-1455672019-01-25T01:23:12Z Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer Yakovlev, P. Klyushin, D. Original contributions Cancer, inflammation and immune surveillance recruit lymphocytes as common key cellular players. The aim of the study was to assess a utility of the absolute and relative lymphocyte counts (ALC and RLC) in peripheral blood of patients with urological cancer as sensitive tool in pretreatment assessment of patient, which correlates with postoperative outcome of the disease, and outlines the overall reactivity of the patient. Materials and Methods: We retrospectively studied correlation between lymphocyte count in peripheral blood of the patients with urological cancer (n = 789) and number of clinical parameters: cancer localization, stage of the disease, treatment outcome, complications. Mann — Whitney two-tailed test and logistic regression models were used. Results: Lymphocyte counts (both absolute and relative) correlate with the cancer stage, and status of the disease, allowing differentiate patients with urological cancer, from healthy individuals, and from the cancer patients after radical surgery. In patients with kidney and bladder cancer, lymphocyte count allowed differentiate the stages of the disease. Lower rate of the reactivity of the patient to the cancer treatment is accurately predicted by the ALC and RLC: those in highest quartile for lymphocytes count have shorter postoperative recovery. Patients in lowest quartile demonstrated worst postoperative performance, including cases of early postoperative mortality due to weak somatic status. Conclusion: The study presents evidence that pretreatment lymphocyte count in the peripheral blood of patients with urological cancer is a sensitive marker of cancer stage, and the reactivity of the patient to the cancer treatment, which can be used in the pretreatment assessment of the patient. Key Words: urological cancer, lymphocytes, postoperative morbidity, reactivity, immune status assessment, treatment outcome. 2018 Article Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer / P. Yakovlev, D. Klyushin // Experimental Oncology. — 2018 — Т. 40, № 2. — С. 119–123 — Бібліогр.: 17 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/145567 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| institution |
Digital Library of Periodicals of National Academy of Sciences of Ukraine |
| collection |
DSpace DC |
| language |
English |
| topic |
Original contributions Original contributions |
| spellingShingle |
Original contributions Original contributions Yakovlev, P. Klyushin, D. Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer Experimental Oncology |
| description |
Cancer, inflammation and immune surveillance recruit lymphocytes as common key cellular players. The aim of the study was to assess a utility of the absolute and relative lymphocyte counts (ALC and RLC) in peripheral blood of patients with urological cancer as sensitive tool in pretreatment assessment of patient, which correlates with postoperative outcome of the disease, and outlines the overall reactivity of the patient. Materials and Methods: We retrospectively studied correlation between lymphocyte count in peripheral blood of the patients with urological cancer (n = 789) and number of clinical parameters: cancer localization, stage of the disease, treatment outcome, complications. Mann — Whitney two-tailed test and logistic regression models were used. Results: Lymphocyte counts (both absolute and relative) correlate with the cancer stage, and status of the disease, allowing differentiate patients with urological cancer, from healthy individuals, and from the cancer patients after radical surgery. In patients with kidney and bladder cancer, lymphocyte count allowed differentiate the stages of the disease. Lower rate of the reactivity of the patient to the cancer treatment is accurately predicted by the ALC and RLC: those in highest quartile for lymphocytes count have shorter postoperative recovery. Patients in lowest quartile demonstrated worst postoperative performance, including cases of early postoperative mortality due to weak somatic status. Conclusion: The study presents evidence that pretreatment lymphocyte count in the peripheral blood of patients with urological cancer is a sensitive marker of cancer stage, and the reactivity of the patient to the cancer treatment, which can be used in the pretreatment assessment of the patient. Key Words: urological cancer, lymphocytes, postoperative morbidity, reactivity, immune status assessment, treatment outcome. |
| format |
Article |
| author |
Yakovlev, P. Klyushin, D. |
| author_facet |
Yakovlev, P. Klyushin, D. |
| author_sort |
Yakovlev, P. |
| title |
Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer |
| title_short |
Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer |
| title_full |
Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer |
| title_fullStr |
Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer |
| title_full_unstemmed |
Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer |
| title_sort |
lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer |
| publisher |
Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України |
| publishDate |
2018 |
| topic_facet |
Original contributions |
| url |
http://dspace.nbuv.gov.ua/handle/123456789/145567 |
| citation_txt |
Lymphocyte count in peripheral blood is a sensitive tool in pretreatment assessment of patients with urological cancer / P. Yakovlev, D. Klyushin // Experimental Oncology. — 2018 — Т. 40, № 2. — С. 119–123 — Бібліогр.: 17 назв. — англ. |
| series |
Experimental Oncology |
| work_keys_str_mv |
AT yakovlevp lymphocytecountinperipheralbloodisasensitivetoolinpretreatmentassessmentofpatientswithurologicalcancer AT klyushind lymphocytecountinperipheralbloodisasensitivetoolinpretreatmentassessmentofpatientswithurologicalcancer |
| first_indexed |
2025-07-10T21:58:16Z |
| last_indexed |
2025-07-10T21:58:16Z |
| _version_ |
1837298852740202497 |
| fulltext |
Experimental Oncology 40, 119–123, 2018 (June) 119
LYMPHOCYTE COUNT IN PERIPHERAL BLOOD IS A SENSITIVE TOOL
IN PRETREATMENT ASSESSMENT OF PATIENTS WITH UROLOGICAL
CANCER
P. Yakovlev1, D. Klyushin2
1Department of Urology, Bogomolets National Medical University, Kyiv 01601, Ukraine
2Department of Computer Science and Cybernetics, Taras Shevchenko National University of Kyiv,
Kyiv 03680, Ukraine
Cancer, inflammation and immune surveillance recruit lymphocytes as common key cellular players. The aim of the study was
to assess a utility of the absolute and relative lymphocyte counts (ALC and RLC) in peripheral blood of patients with urological
cancer as sensitive tool in pretreatment assessment of patient, which correlates with postoperative outcome of the disease, and
outlines the overall reactivity of the patient. Materials and Methods: We retrospectively studied correlation between lymphocyte
count in peripheral blood of the patients with urological cancer (n = 789) and number of clinical parameters: cancer localization,
stage of the disease, treatment outcome, complications. Mann — Whitney two-tailed test and logistic regression models were used.
Results: Lymphocyte counts (both absolute and relative) correlate with the cancer stage, and status of the disease, allowing dif-
ferentiate patients with urological cancer, from healthy individuals, and from the cancer patients after radical surgery. In patients
with kidney and bladder cancer, lymphocyte count allowed differentiate the stages of the disease. Lower rate of the reactivity of the
patient to the cancer treatment is accurately predicted by the ALC and RLC: those in highest quartile for lymphocytes count have
shorter postoperative recovery. Patients in lowest quartile demonstrated worst postoperative performance, including cases of early
postoperative mortality due to weak somatic status. Conclusion: The study presents evidence that pretreatment lymphocyte count
in the peripheral blood of patients with urological cancer is a sensitive marker of cancer stage, and the reactivity of the patient
to the cancer treatment, which can be used in the pretreatment assessment of the patient.
Key Words: urological cancer, lymphocytes, postoperative morbidity, reactivity, immune status assessment, treatment outcome.
Cancer progression, chronic inflammation and
strength of immune response are the phenomena
tightly connected and interrelated in a diseased per-
son [1, 2]. Each of entities either predisposes, main-
tains, or facilitates the progression of each of those
conditions, in particular, chronic inflammation serves
as basis for cancer initiation, cancer progression
causes suppression of the immune system, includ-
ing induction of apoptosis of T-lymphocytes [3–5],
immunosuppression facilitates carcinogenesis [3].
The cellular (white blood cells) and molecular (cy-
tokines, chemokines) mediators are common for all
those three processes, which make them universal
indicators of the state of the disease and reactivity
of the patient.
The assessment of the patients’ reactivity
is an important step in managing urological ma-
lignancy, as it relates to the ability to recover after
the planned treatment, have less postoperative
complications and shorter stay after surgery [6].
It is well known that any modality in cancer treat-
ment bears the immunosuppressive potential.
Thus, knowledge of the basic reactivity of the pa-
tient and scope of its ability to cope with the stress
caused by cancer itself and cancer treatment can
be additional study in pretreatment clinical evalu-
ation of the patient.
The aim of the study was to validate the absolute
and relative count of lymphocytes in peripheral blood
in patients prior to surgical treatment as sensitive and
informative tool in pretreatment assessment of the
patient, which correlates with postoperative outcome
of the disease, and outlines the overall reactivity of the
patient.
MATERIALS AND METHODS
We retrospectively studied the medical records
of 789 patients who during 2014–2016 received sur-
gical treatment at the Department of Urology for uro-
logical cancer. The study objects included: 1) blood
analysis before treatment, in particular, absolute
lymphocyte count (ALC) and relative lymphocyte count
(RLC) — percentage of lymphocytes in relation to all
white blood cells in peripheral blood; 2) final diagnosis
at the discharge; 3) stage of cancer; 4) treatment out-
come, 5) length of postoperative stay. Blood analyses
were performed at the same automatic blood analyzer,
the results entered into a database, and analyzed with
MS Office Excel software.
The study protocol was reviewed and endorsed
by the Ethics Committee.
All patients were distributed into three groups:
group I — 722 patients with primary urological cancer
scheduled to receive cancer treatment; group II —
67 cancer patients who had received radical cancer
treatment more than 3 months ago and at the moment
of this study had no signs of recurrence or progres-
sion, and were considered “recovered”; group III —
62 healthy individuals without cancer, who came to the
Submitted: August 02, 2017.
*Correspondence: E-mail: pavel_3@hotmail.com
Abbreviations used: ALC — absolute lymphocyte count; N/L ratio —
neutrophil-to-lymphocyte ratio; RLC — relative lymphocyte count;
TNM — clinical classification of tumors.
Exp Oncol 2018
40, 2, 119–123
120 Experimental Oncology 40, 119–123, 2018 (June)
clinic for a regular check-up. The results of their blood
analysis were considered as control group for the
purpose of this study.
We used the data from these three groups to con-
duct mathematical analysis of correlation between
the status of the disease (primary urological cancer,
recovered cancer patients, and cancer-free patients)
and lymphocyte counts in peripheral blood. We applied
Mann — Whitney two-tailed test with a significance
level of 0.05 to assess if difference exists between
study groups based on the investigated countable
parameters (ALC and RLC).
At the second part of our study we focused only
on the patients from the group I — those with most
frequent urological cancer (urinary bladder, prostate,
kidney) — to test if ALC and RLC may differentiate the
stage of the cancer. Table 1 presents the distribution
of patients among the cancer types. Table 2 presents
the distribution of patients with most frequent cancer
per stage based on TNM classification.
Table 1. Localization of urological tumors in the study group
Tumors Number of patients
Urinary bladder cancer 269
Kidney cancer 140
Prostate cancer 138
Testicular cancer 87
Penile cancer 21
Renal pelvis cancer 20
Adrenal gland cancer 7
Sarcoma 6
Ureteral cancer 4
Multiple tumors of urological organs 30
Total 722
Table 2. Distribution of patients by tumor localization and TNM stage
Localization, stage Number of patients
Urinary bladder
Stage I 170
Stage II 43
Stage III 32
Stage IV 24
Subtotal 269
Kidney
Stage I 59
Stage II 35
Stage III 26
Stage IV 20
Subtotal 140
Prostate
Stage I 1
Stage II 55
Stage III 43
Stage IV 39
Subtotal 138
TOTAL 547
We applied Mann — Whitney two-tailed test to each
pair of stages (I and II, I and III, etc.) in every cancer
type subgroup to assess if difference exists between
study population of particular stage in each cancer
type subgroup based on the ALC and RLC.
To assess the correlation between preoperative lym-
phocyte count and length of postoperative stay we used
the data on 35 patients with kidney cancer of stage II who
underwent radical nephrectomy. The model of binary
logistic regression was used for this purpose.
RESULTS
Mean ALC and RLC in study groups (I, II, III) are pre-
sented in Tables 3, 4, and points at evident differences
in these indexes between study groups. In particular, the
lowest ALC and RLC values were observed in the group
of cancer patients, and the highest — in cancer patients
after radical treatment. This fact highlights the suppres-
sive effect of the tumor on lymphopoetic branch, and
stimulatory effect on myeloid lineage of hemopoesis,
which maintains the inflammatory state. Surgical removal
of the tumor, even in the setting of the stage IV patients
with cytoreductive purpose, leads to correction of the
lymphocytes count in the blood analysis, which even
exceeds such of the healthy control patients (group III).
Based on these data we can acknowledge that surgical
removal of the tumorous tissue reduces the immunosup-
pressive effect of the cancer, and on other hand, allevi-
ates the inflammatory effect of the tumor on the body.
Table 3. Mean ALC in peripheral blood in groups I–III, •103/ml
Group Number
of patients
ALC Standard
deviationMinimum Maximum Mean
I Primary can-
cer before
treatment
722 0.3 4.1 1.720 0.548
II Cancer af-
ter definitive
treatment
67 1.0 4.5 2.034 0.755
III Healthy con-
trols
62 1.0 3.6 1.974 0.582
Table 4. Mean RLC in peripheral blood of total white blood cell count in pe-
ripheral blood in groups I–III, %
Group Number
of patients
RLC Standard
deviationMinimum Maximum Mean
I Primary can-
cer before
treatment
722 5.8 59.7 27.890 8.647
II Cancer af-
ter definitive
treatment
67 16.7 60.0 32.888 8.874
III Control 62 13.6 48.8 32.294 7.504
To evaluate if patients’ study groups (I, II, and III)
differ by mean absolute and relative level of lympho-
cytes in peripheral blood, we ran Mann — Whitney
two-tailed test for ALC and RLC for each pair of com-
parison. The results are presented in Tables 5, 6.
Table 5. Results of Mann — Whitney two-tailed test for mean ALC in periphe-
ral blood in paired study groups
Criteria Pairs of patients’ groups for comparison
I–II I–III II–III
U 10,893.500 9280.000 724.000
Expected value 14,340.000 12,547.500 700.000
Variance (U) 1,804,682.55 1,568,879.1 8818.613
p-value (two-tailed) 0.010 0.009 0.802
Alpha 0.05 0.05 0.05
Table 6. Results of Mann — Whitney two-tailed test for RLC in peripheral
blood in paired study groups
Criteria Pairs of patients’ groups for comparison
I–II I–III II–III
U 9777.000 8518.000 727.000
Expected value 14,340.000 12,547.500 700.000
Variance (U) 1,811,568.207 1,574,665.593 8864.901
p-value (two-tailed) 0.001 0.001 0.778
Alpha 0.05 0.05 0.05
Table 5 data indicate that there is statistically sig-
nificant difference in mean ALC count in peripheral
blood between cancer patients and healthy controls
(1.72 • 103/ml vs 1.97 • 103/ml, р = 0.009), and can-
cer patients and those who received radical cancer
treatment (1.72 • 103/ml vs 2.03 • 103/ml, р = 0.01).
Experimental Oncology 40, 119–123, 2018 (June) 121
Cancer patients after radical treatment do not sta-
tistically differ in their ALC from the healthy controls
(2.03 • 103/ml vs 1.97 • 103/ml, р = 0.8).
The data from Table 6 demonstrate statistically
significant difference in RLC between cancer patients
and healthy controls (27.9% vs 32.3%, р = 0.001), and
between cancer patients and cancer patients after
radical treatment (27.9% vs 32.9%, р = 0.001). As with
ALC, the RLC in cancer patients after radical treatment
does not differ from such in healthy controls (32.9%
vs 32.3%, р = 0.78).
In order to answer the question if ALC and RLC
can differentiate clinical stages (I, II, III or IV) in each
type of cancer (urinary bladder, prostate and kidney)
we determined mean for each parameter, and then
performed Mann — Whitney two-tailed test for each
pair of clinical stages. The results are presented
in Table 7.
Table 7. ALC and RLC in peripheral blood in most frequent urological can-
cer types per TMN stage
Can-
cer and
stage
Pa-
tients,
n
Minimum
ALC,
• 103/ml
Maxi-
mum
ALC,
• 103/ml
Mean
ALC,
• 103/ml
Mini-
mum
RLC
Max-
imum
RLC
Mean
RLC, %
Urinary bladder cancer
Stage I 170 0.300 3.900 1.777 7.500 53.000 29.529
Stage II 43 0.500 2.600 1.702 6.900 45.600 25.391
Stage III 32 0.700 3.500 1.816 11.400 39.600 25.803
Stage IV 24 0.500 3.100 1.596 8.700 43.600 23.271
Subtotal 269
Kidney cancer
Stage I 59 0.800 2.900 1.861 16.200 59.700 31.880
Stage II 35 0.900 2.600 1.654 15.400 45.000 27.786
Stage III 26 0.900 3.300 1.762 14.300 43.600 27.986
Stage IV 20 0.400 2.900 1.555 7.400 44.400 22.690
Subtotal 140
Prostate cancer
Stage I 1 − − 1.6 − − 26.7
Stage II 55 0.600 3.000 1.669 9.200 54.200 28.782
Stage III 43 0.700 4.100 1.799 14.100 53.400 29.395
Stage IV 39 0.700 3.400 1.544 12.700 42.500 26.372
Subtotal 138
TOTAL 547
The data from Table 7 indicate that in all urologi-
cal malignancies with progressing clinical stage one
can observe the drop in absolute and relative number
of lymphocytes in peripheral blood, favoring rise
in neutrophil granulocytes. These data support the
notion that progression of cancer occurs against pro-
gressing immunosuppression, reflected in declining
level of lymphocytes.
The results of Mann — Whitney two-tailed test as-
sessing the significance of difference in ALC and RLC
between stages I through IV in each type of cancer are
presented in Tables 8–10 in binary fashion (“Yes” —
there is difference, “No” — there is no difference).
Table 8. Difference in ALC and RLC between clinical stages of urinary
bladder cancer cases
Cancer stage I II III IV
ALC RLC ALC RLC ALC RLC ALC RLC
I — — No Yes No Yes No Yes
II — — — — No No No No
III — — — — — — No No
IV — — — — — — — —
Note: RLC proved to be a valid criterion allowing differentiate patients with
stage I bladder cancer from all others. To date, patients with bladder cancer
of stage II–IV had RLC lower than in stage I.
Table 9. Difference in ALC and RLC between clinical stages of prostate
cancer cases
Cancer
stage
I II III IV
ALC RLC ALC RLC ALC RLC ALC RLC
I — — — — — — — —
II — — — — No No No No
III — — — — — — No No
IV — — — — — — — —
Table 10. Difference in ALC and RLC between clinical stages of kidney
cancer cases
Cancer
stage
I II III IV
ALC RLC ALC RLC ALC RLC ALC RLC
I — — Yes Yes No Yes Yes Yes
II — — — — No No No Yes
III — — — — — — No No
IV — — — — — — — —
Note: ALC and RLC in patients.
From the data presented in Table 8, we can con-
clude that for patients with bladder cancer the mean
ALC may not differentiate stages of the cancer. Con-
trary, there is statistically significant difference for
RLC between stage I and others stages. This means
that the patients with bladder cancer of stage I have
the highest RLC. Starting with stage II and up the RLC
difference loses significance.
Table 9 represents the data on prostate cancer
cases. Neither ALC nor RLC in peripheral blood of pa-
tients with prostate cancer play a role of valid diffe-
rentiation tool between stages. As there was only one
patient with stage I prostate cancer, his data could not
be included in calculation.
Table 10 demonstrates that in patients with kidney
cancer ALC and RLC are of higher differentiating value,
in particular, ALC allows differentiate stages I and II,
and I and IV stage, while RLC allows differentiate
stages I and all others (II, III and IV), and stages II and IV.
DISCUSSION
In routine clinical practice we use different quali-
tative and quantitative criteria and parameters which
describe the somatic condition of the patient. We need
to know how fit the patient is for the treatment. We also
need to know how reactive the patient is, meaning how
much resources patient has for recovering from the
trauma caused by cancer treatment, how probable the
complications are and what would be the anticipated
length of postoperative stay.
It is commonly accepted and validated in the lit-
erature that ALC and neutrophil-to-lymphocyte (N/L)
ratio are valid prognostic factors for survival in cancer
patients [7–12]. The cut-off value for ALC is above
1.3 • 103/ml, and for N/L ratio is below 2.4. The nor-
mal range for RLC in peripheral blood is above 19%.
Falling ALC or rising N/L ratio (dropping RLC) are
considered as predictors of poor prognosis, cancer
progression, recurrence, or unfavorable treatment
outcome. This statement reflects the notion that de-
velopment of cancer occurs against lymphocytopenia
and neutrophilia. Neutrophils are the cells producing
pro-angiogenic, anti-apoptotic and diverse growth
factors, whereas lymphocytes are cells yielding innate
and adoptive immunity against cancer cells.
122 Experimental Oncology 40, 119–123, 2018 (June)
Another research has long time ago postulated and
validated [13] that absolute and relative counts of lym-
phocytes in peripheral blood are reliable indicators of re-
activity of the organism and strength of immune system
response required for combatting the disease. It was
demonstrated, that “stress” (reaction of the physiologi-
cal systems to the extreme forces affecting the body)
causes extreme lymphopenia below the cut-off thresh-
old of 1.3 • 103/ml for ALC, or 19% for RLC. Whereas fac-
tors less extreme and less stressful might lead to milder
reaction of the immune system, which range from soft
immunosuppression (falling ALC and RLC to above
1.3 • 103/ml, or 19%) to even stimulation of immune
reactivity (ALC and RLC rise to the upper limits of the
normal range). The countable criterion, which reflects
this phenomenon is relative count of lymphocytes in pe-
ripheral blood, thus making RLC a valuable diagnostic
tool readily available in clinical blood test.
Study of urinary bladder carcinoma yielded valu-
able understanding of how cancer and immunity inter-
act. Bladder carcinomas have developed a mechanism
to avoid immune-induced apoptosis [5]. Under normal
conditions the Fas/Fas-ligand system mediates pro-
grammed cell death in cancerous tissues. Fas ligand
is found primarily on T-lymphocytes and natural
killer (NK) cells [14, 15]. Fas activation via binding
of Fas ligand results in apoptosis of the cell bearing
the receptor. Bladder carcinomas have developed
a mechanism to avoid this immune response by remov-
ing Fas, effectively evading apoptosis [5]. Additionally,
it has been shown that high-grade bladder cancers
have developed resistance to Fas-ligand-induced
apoptotic events downstream of Fas. It has been sug-
gested that the production and secretion of soluble Fas
(sFas), produced by all bladder cancer cell lines may
be able to block the action of T-lymphocytes and even
induce apoptosis in immune cells [3, 5], reducing level
of T cells in the peripheral blood.
Assessment of the immune status is not yet a rou-
tine practice in cancer clinic. The data presented above
highlight that suppression of immune surveillance
promotes the development and progression of cancer,
which makes the immunological study a vital diagnos-
tic tool in the arsenal of oncologist.
The assessment of the immune status can be done
at different levels of complexity: 1) basic blood analysis
(which was used for this study), 2) analysis of cellular
fractions (lymphocytes), functional cellular activity and
humoral aspects of immune system (immunogram),
3) HLA-phenotyping of lymphocytes to assess the
defects in antigen-presentation machinery [16, 17].
All of those methods deliver particular diagnostic
value to the assessment of immune system at rising
cost and with rising level of accuracy. It is important
to combine all available diagnostic tools. Still we need
to acknowledge that the simplest and always readily
available test — blood analysis — delivers accurate
and valid data about the strength of immune surveil-
lance and reactivity of the patient, which may guide
the clinical judgment. To illustrate this, out of our
dataset, four patients with cancer of stage IV and
lowest lymphocyte counts — ALC = 0.3–0.5 • 103/ml,
and RLC% = 7.5–9.0 died in 3–4 weeks after surgery.
At the same time, most of the patients with highest
preoperative ALC and RLC had shortest postoperative
stay compared to other patients after similar surgical
procedures, but with worse results of ALC and RLC.
Based on this observation and on the results of our
study, we can conclude that ALC and RLC in peripheral
blood of patients with urological cancer are efficient
and valid criteria, which allow to differentiate patients
with urological cancer from those who were radically
treated from cancer, and from those who are healthy.
For the purpose of differentiating stages of the cancer,
ALC and RLC are valid tools in some cases, such as:
RLC differentiates stage I bladder cancer from the
rest of stages; in kidney cancer ALC differentiates
stage I and stage II, and I and IV, RLC — stage I from
all others, and stage II from IV.
The reactivity of the patient’s immune system
converts into outcome of the cancer treatment. The
patients with highest preoperative ALC and RLC per-
formed best and had shortest postoperative stay, and
those with lowest ALC and RLC demonstrated poorest
results of postoperative stay and recovery, including
four postoperative deaths during month after surgery
for urological cancer.
CONCLUSION
ALR and RLC in peripheral blood are valid and sen-
sitive tests easily available in everyday clinical practice,
correlating with the cancer stage and reflecting the
progress, or status of the disease. The results of these
tests allow to differentiate patients with urological
cancer from healthy individuals, and from the cancer
patients after radical surgery. Lymphocyte counts
(both absolute and relative) are higher in patients af-
ter radical cancer treatment than in healthy controls,
which signify immune-stimulative effect of radical
surgical excision of the tumor and reduction of its im-
munosuppressive effect. In patients with kidney and
bladder cancer, lymphocyte count allows differentiate
the stages of the disease. The reactivity of the patient
to the cancer treatment is accurately predicted by the
ALR and RLC: those in highest quartile for ALC and RLC
(above 2 • 103/ml, and above 32%, respectively) have
shorter postoperative recovery and no postoperative
complications. Patients with lowest ALC and RLC
(below 1.3 • 103/ml, and below 19%, respectively)
demonstrated worst postoperative performance,
including cases of early postoperative mortality due
to weak somatic status.
REFERENCES
1. Grivennikov S, Greten FR, Karin M. Immunity, inflam-
mation, and cancer. Cell 2010; 140: 883–99.
2. Hanahan D, Weinberg RA. Hallmarks of cancer: the
next generation. Cell 2011; 144: 646–74.
3. Thompson DB, Siref LE, Feloney MP, et al. Immu-
nological basis in the pathogenesis and treatment of bladder
cancer. Expert Rev Clin Immunol 2015; 11: 265–79.
Experimental Oncology 40, 119–123, 2018 (June) 123
4. Mizutani Y, Yoshida O, Miki T. Adriamycin-mediated
potentiation of cytotoxicity against freshly isolated bladder
cancer cells by autologous non-activated peripheral blood
lymphocytes and tumor infiltrating lymphocytes. J Urol
1999; 162: 2170–5.
5. Perabo FG, Kamp S, Schmidt D, et al. Bladder cancer
cells acquire competent mechanisms to escape Fas-mediated
apoptosis and immune surveillance in the course of malignant
transformation. Br J Cancer 2001; 84: 1330–8.
6. Clavien PA, Barkun J, de Oliveira ML, et al. The
Clavien-Dindo classification of surgical complications: five-
year experience. Ann Surg 2009; 250: 187–96.
7. Kim HS, Ku JH. Systemic inflammatory response based
on neutrophil-to-lymphocyte ratio as a prognostic marker
in bladder cancer. Dis Markers 2016; Article ID 8345286: 1–12.
8. Mano R, Baniel J, Shoshany O. Neutrophil-to-lympho-
cyte ratio predicts progression and recurrence of non-muscle-
invasive bladder cancer. Urol Oncol 2015; 33: e1–7.
9. Morgan TM. Editorial Comment to: Saroha S,
Uzzo RG, Plimack ER, et al. Lymphopenia is an independent
predictor of inferior outcome in clear cell renal carcinoma.
J Urol 2013; 189: 460.
10. Motzer RJ, Bacik J, Schwartz LH, et al. Prognostic
factors for survival in previously treated patients with metastatic
renal cell carcinoma. J Clin Oncol 2004; 22: 454–63.
11. Ohno Y, Nakashima J, Ohori M, et al. Pretreatment
neutrophil-to-lymphocyte ratio as an independent predictor
of recurrence in patients with nonmetastatic renal cell carci-
noma. J Urol 2010; 184: 873–8.
12. Ozyalvacli ME, Ozyalvacli G, Kocaaslan R, et al.
Neutrophil-lymphocyte ratio as a predictor of recurrence and
progression in patients with high-grade pT1 bladder cancer.
Can Urol Assoc J 2015; 9: 126–31.
13. Garkavi LK, Kvakina EB, Kuzmenko TS. Antistress
reactions of activation therapy. Reaction of activation as a way
towards the health through the process of self-organization.
М: Imedis, 1998. 656 p. (in Russian).
14. Gruss HJ. Molecular, structural, and biological char-
acteristics of the tumor necrosis factor ligand superfamily. Int
J Clin Lab Res 1996; 26: 143–59.
15. Chicheportiche Y, Bourdon PR, Xu H, et al. TWEAK,
a new secreted ligand in the tumor necrosis factor family that
weakly induces apoptosis. J Biol Chem 1997; 272: 32401–10.
16. Aptsiauri N, Garcia-Lora AM, Cabrera T. MHC
Class I antigens in malignant cells: immune escape and re-
sponse to immunotherapy. Briefs in Cancer Research 6. New
York: Springer, 2013. 59 p.
17. Drannik GN, Drannik AG. Introduction in clinical
immunology. Handbook for Students. K: Yuston, 2015. 200 p.
(in Russian).
Copyright © Experimental Oncology, 2018
|