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THE IMPAIRED PRODUCTION OF TNF, TGF BETA 1 AS AN IMPORTANT REASON OF DEFECTIVE NATURAL KILLER ABILITY IN NON-HODGKIN LYMPHOMA PATIENTS WITH SPLEEN AFFECTION
Author(s): ,
Vira Barilka
Affiliations:
Immunology and Genetics of Blood Neoplasms Lviv, Ukraine,SI Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine,Lviv,Ukraine
,
Volodymyr Matlan
Affiliations:
Department of Hematology and Transfusiology,Danylo Halytsky National Medical University, Lviv, Ministry of Health of Ukraine,Lviv,Ukraine
,
Olha Shalay
Affiliations:
Immunology and Genetics of Blood Neoplasms Lviv, Ukraine,SI Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine,Lviv,Ukraine
,
Yuriy Yevstachevych
Affiliations:
Immunology and Genetics of Blood Neoplasms Lviv, Ukraine,SI Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine,Lviv,Ukraine
,
Sophiya Prymak
Affiliations:
Immunology and Genetics of Blood Neoplasms Lviv, Ukraine,SI Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine,Lviv,Ukraine
Volodymyr Loginsky
Affiliations:
Immunology and Genetics of Blood Neoplasms Lviv, Ukraine,SI Institute of Blood Pathology and Transfusion Medicine of the NAMS of Ukraine,Lviv,Ukraine
(Abstract release date: 05/17/18) EHA Library. Barilka V. 06/14/18; 216599; PB2344
Mrs. Vira Barilka
Mrs. Vira Barilka
Contributions
Abstract

Abstract: PB2344

Type: Publication Only

Background

The microenvironment of non-Hodgkin lymphoma (NHL) may assists to distribution and survival of neoplastic cells with simultaneous development of immune tolerance of natural killer (NK) by broken secretion of tumor necrosis factor (TNF) and transforming growth factor beta 1 (TGFβ1).

Aims

Тo detect the cytotoxicity ability (CA) of NK from mononuclear cells (MN) of peripheral blood (MNPB), MN of lymphatic nodes from the gate of spleen (MNLNs), MN from spleen tissue (MNS) of 10 NHL patients (pts) with spleen affections. To detect the СА NK from peripheral blood (as an effector cells) of NHL pts vs. autological MNS, MNLNs (as a target). Тo prepare supernatants (Sp) of the MNPB, MNLN and MNS after 24 h incubation cells in RPMI 1640 and to detect the concentration of cytokines in Sp and plasma. 

Methods

The peripheral blood gained before breakfast. The tissues both of lymph nodes and spleen obtained after surgical remover. The concentrations of TNF and TGFβ1 were determinatend by biological methods. The CA of NK was estimated vs. К562 and autological NHL cells marked with 3Н-methylthymidine. Control group consisted of 15 healthy persons and 8 pts with reactive hyperplasia of spleen (RHS) and 7 pts  - with non-specific reactive lymphadenitis (nSRL).

Results

The level of TNF in both plasma and Sp MNPB of NHL pts were higher, than in the plasma and Sp MNPB of the healthy donors (р<0,001). The TNF levels in both Sp of MNS (0,23±0,12 ng/ml) and MNLNs (0,19±0,07 ng/ml) of NHL pts did not differ statistically and were exceeded by analogical data in RHS pts and nSRL. The level of TGF β1 in plasma (3,68±0,73 ng/ml) NHL pts was higher (3,730±0,900 ng/ml) than in control group (р<0,05). TGFβ1 in Sp of MNPB was two times lower that of control (p<0,05). The level of TGFβ1 in Sp of MCS of NHL pts was for certain below (4,860±0,610 ng/ml), than in Sp of MCS of RHS pts (8,330±0,531 ng/ml; р<0,05). The CA of NK from МNS vs. K562 was higher (29,27±7,92 %) than in both МNLNs (15,85±3,80%; p<0,05) and МNPB in NHL pts (16,69±2,26%; p<0,05). The CA of NK from peripheral blood of NHL pts was for certain below (14,695±2,26%) than in healthy donors (22,241±0,84%; р<0,05). The CA of NK from МNLNs was lower vs. К562 cells line, than CA of NK from MNS of NHL pts with spleen affections. The СА of NK from blood vs. the autological МNLNs and MNS were in both cases for certain below, than CA of NK vs the of К562 cell lines (р<0,01). The CA of NK from blood NHL pts vs. autological of MNS (5,36±1,64%) and МCLNs (7,26±1,60%) were statisticall  below, than data of autological CA of NK in the RHS pts (30,175±2,94; р<0,001). The CA of NK from blood of NHL pts negatively correlated with the соncentration of TNF in both plasma (r= - 0,50) and Sp of MNPB (r= - 0,55). It should be noted that the level of TNF in plasma of pts with RHS positively correlated with CA of NK from МNS (r = 0,40). The CA of NK from MNPB of NHL pts negatively correlated with the concentration of TGF β1 in plasma (r = - 0,619) and negatively with the TGF β1 in Sp from MNS (r= - 0,620).

Conclusion

Concentration of TNF and TGFβ1 in plasma of NHL pts with spleen affection for certain higher, than in the healthy persons.  NK from blood of NHL pts vs. own neoplastic cells was lower than stranger К562. These results could specify on tolerance of cellular immunity in the NHL pts. Thus, impaired secretion of TNF and TGF β1 may has an important role in the regulation of ability NK vs. neoplastics cells and can be important markers for modulation of immune responses in NHL pts with spleen affection.

Session topic: 19. Non-Hodgkin lymphoma Biology & Translational Research

Keyword(s): Natural killer, Non-Hodgkin's lymphoma, Transforming growth factor-, Tumor necrosis factor (TNF)

Abstract: PB2344

Type: Publication Only

Background

The microenvironment of non-Hodgkin lymphoma (NHL) may assists to distribution and survival of neoplastic cells with simultaneous development of immune tolerance of natural killer (NK) by broken secretion of tumor necrosis factor (TNF) and transforming growth factor beta 1 (TGFβ1).

Aims

Тo detect the cytotoxicity ability (CA) of NK from mononuclear cells (MN) of peripheral blood (MNPB), MN of lymphatic nodes from the gate of spleen (MNLNs), MN from spleen tissue (MNS) of 10 NHL patients (pts) with spleen affections. To detect the СА NK from peripheral blood (as an effector cells) of NHL pts vs. autological MNS, MNLNs (as a target). Тo prepare supernatants (Sp) of the MNPB, MNLN and MNS after 24 h incubation cells in RPMI 1640 and to detect the concentration of cytokines in Sp and plasma. 

Methods

The peripheral blood gained before breakfast. The tissues both of lymph nodes and spleen obtained after surgical remover. The concentrations of TNF and TGFβ1 were determinatend by biological methods. The CA of NK was estimated vs. К562 and autological NHL cells marked with 3Н-methylthymidine. Control group consisted of 15 healthy persons and 8 pts with reactive hyperplasia of spleen (RHS) and 7 pts  - with non-specific reactive lymphadenitis (nSRL).

Results

The level of TNF in both plasma and Sp MNPB of NHL pts were higher, than in the plasma and Sp MNPB of the healthy donors (р<0,001). The TNF levels in both Sp of MNS (0,23±0,12 ng/ml) and MNLNs (0,19±0,07 ng/ml) of NHL pts did not differ statistically and were exceeded by analogical data in RHS pts and nSRL. The level of TGF β1 in plasma (3,68±0,73 ng/ml) NHL pts was higher (3,730±0,900 ng/ml) than in control group (р<0,05). TGFβ1 in Sp of MNPB was two times lower that of control (p<0,05). The level of TGFβ1 in Sp of MCS of NHL pts was for certain below (4,860±0,610 ng/ml), than in Sp of MCS of RHS pts (8,330±0,531 ng/ml; р<0,05). The CA of NK from МNS vs. K562 was higher (29,27±7,92 %) than in both МNLNs (15,85±3,80%; p<0,05) and МNPB in NHL pts (16,69±2,26%; p<0,05). The CA of NK from peripheral blood of NHL pts was for certain below (14,695±2,26%) than in healthy donors (22,241±0,84%; р<0,05). The CA of NK from МNLNs was lower vs. К562 cells line, than CA of NK from MNS of NHL pts with spleen affections. The СА of NK from blood vs. the autological МNLNs and MNS were in both cases for certain below, than CA of NK vs the of К562 cell lines (р<0,01). The CA of NK from blood NHL pts vs. autological of MNS (5,36±1,64%) and МCLNs (7,26±1,60%) were statisticall  below, than data of autological CA of NK in the RHS pts (30,175±2,94; р<0,001). The CA of NK from blood of NHL pts negatively correlated with the соncentration of TNF in both plasma (r= - 0,50) and Sp of MNPB (r= - 0,55). It should be noted that the level of TNF in plasma of pts with RHS positively correlated with CA of NK from МNS (r = 0,40). The CA of NK from MNPB of NHL pts negatively correlated with the concentration of TGF β1 in plasma (r = - 0,619) and negatively with the TGF β1 in Sp from MNS (r= - 0,620).

Conclusion

Concentration of TNF and TGFβ1 in plasma of NHL pts with spleen affection for certain higher, than in the healthy persons.  NK from blood of NHL pts vs. own neoplastic cells was lower than stranger К562. These results could specify on tolerance of cellular immunity in the NHL pts. Thus, impaired secretion of TNF and TGF β1 may has an important role in the regulation of ability NK vs. neoplastics cells and can be important markers for modulation of immune responses in NHL pts with spleen affection.

Session topic: 19. Non-Hodgkin lymphoma Biology & Translational Research

Keyword(s): Natural killer, Non-Hodgkin's lymphoma, Transforming growth factor-, Tumor necrosis factor (TNF)

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