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CD39 EXPRESSION ON CD4 T INFILTRATING LYMHOCYTES IN THE TUMOR MICROENVIRONMENT OF LYMPHOMAS
Author(s): ,
Rosa Di Gaetano
Affiliations:
Haematology,Hospital,Castelfranco Veneto,Italy
,
Valentina Gasparetto
Affiliations:
Haematology,Hospital,Castelfranco Veneto,Italy
,
Barbara Callegari
Affiliations:
Haematology,Hospital,Castelfranco Veneto,Italy
,
Maria Angela De Benedetto
Affiliations:
Haematology,Hospital,Castelfranco Veneto,Italy
,
Antonio Scapinello
Affiliations:
Pathology,Hospital,Castelfranco Veneto,Italy
Giuseppe Tagariello
Affiliations:
Haematology,Hospital,Castelfranco Veneto,Italy
(Abstract release date: 05/19/16) EHA Library. Di Gaetano R. 06/09/16; 134945; PB2045
Dr. Rosa Di Gaetano
Dr. Rosa Di Gaetano
Contributions
Abstract
Abstract: PB2045

Type: Publication Only

Background
In tumor microenvironment (TME) a variety of mechanisms favor a tumor-protection, one of them is the accumulation of extracellular adenosine (ADO) by  up-regulating activity of ectoenzime CD39. The generation  of ADO from ATP metabolism is recognized as a mechanism for immunosuppressive function of regulatoty T cell (Treg), a component  of the  CD4+ T lymphocytes expressing variable  functional molecules  and involved in tumor escape

Aims
It has been well-documented the increase of Treg in various solid tumor and  the higher CD39 expression in some types of human cancer.  We have evaluated the CD39 and the CD26 (an adenosine deaminase) on CD4+T infiltrating lymphocytes in lymph node with  lymphoma to verify the expression of two markers and whether they could be an attractive features for analysis of TME of a non Hodgkin lymphoma (NHL)

Methods
We analyzed by flow cytometry (FC) immunophenotyping non-neoplastic (10) and B-NHL (48) lymph node samples. and we measured the CD26 and CD39 on CD4+ T lymphocytes in all tissues. Among B-NHL were 14 diffuse large B cell lymphoma (DLBCL)  and 3 relapsed

Results
Compared to non-neoplastic samples, CD4+T cells of NHL showed statistically significant difference on CD26 (67% vs 39.5%; p < 0.001) and on CD39 (6% vs 34%; p < 0.001). In NHL, compared to other entities the value of CD26 on DLBCL (39.5% vs 34%) and on the relapsed (39.5% vs 29%) was not significantly different; while CD39 on both groups, DLBCL (34% vs 54%; p <0.005) and relapsed (34% vs 74%; p <0.001), resulted significantly  increased.

Conclusion
Although the regulatory activity of immune system can employ a diversity of molecular mechanisms, the presence of enzymatically-competent CD39 on surface of infiltrating CD4+T suggest that the CD39 pathway can be a distinct mechanism utilized by Treg in TME of lymphomas. Furthermore, the tendency to the  reduction (heightened in the relapsed) of CD26, connectable to a lower activity of adenosine deaminase, beside the up-regulated expression of  CD39, could underlies an increased accumulation of extracellular ADO and its important role in Treg-mediated immune response suppression. Data of DLBCL, resembling the relapsed, tend to differentiate from other entities for a more suppressive functional profile. Together, these simple and fast assays obtained by FC support the finding that ATP-ectonucleotidase-adenosine system may have a role in mediating  Treg activity also  in lymphomas suggesting that  CD39 represents a possible target  for cancer immunotherapy.



Session topic: E-poster

Keyword(s): Lymphoma, Microenvironment, T regulatory cells
Abstract: PB2045

Type: Publication Only

Background
In tumor microenvironment (TME) a variety of mechanisms favor a tumor-protection, one of them is the accumulation of extracellular adenosine (ADO) by  up-regulating activity of ectoenzime CD39. The generation  of ADO from ATP metabolism is recognized as a mechanism for immunosuppressive function of regulatoty T cell (Treg), a component  of the  CD4+ T lymphocytes expressing variable  functional molecules  and involved in tumor escape

Aims
It has been well-documented the increase of Treg in various solid tumor and  the higher CD39 expression in some types of human cancer.  We have evaluated the CD39 and the CD26 (an adenosine deaminase) on CD4+T infiltrating lymphocytes in lymph node with  lymphoma to verify the expression of two markers and whether they could be an attractive features for analysis of TME of a non Hodgkin lymphoma (NHL)

Methods
We analyzed by flow cytometry (FC) immunophenotyping non-neoplastic (10) and B-NHL (48) lymph node samples. and we measured the CD26 and CD39 on CD4+ T lymphocytes in all tissues. Among B-NHL were 14 diffuse large B cell lymphoma (DLBCL)  and 3 relapsed

Results
Compared to non-neoplastic samples, CD4+T cells of NHL showed statistically significant difference on CD26 (67% vs 39.5%; p < 0.001) and on CD39 (6% vs 34%; p < 0.001). In NHL, compared to other entities the value of CD26 on DLBCL (39.5% vs 34%) and on the relapsed (39.5% vs 29%) was not significantly different; while CD39 on both groups, DLBCL (34% vs 54%; p <0.005) and relapsed (34% vs 74%; p <0.001), resulted significantly  increased.

Conclusion
Although the regulatory activity of immune system can employ a diversity of molecular mechanisms, the presence of enzymatically-competent CD39 on surface of infiltrating CD4+T suggest that the CD39 pathway can be a distinct mechanism utilized by Treg in TME of lymphomas. Furthermore, the tendency to the  reduction (heightened in the relapsed) of CD26, connectable to a lower activity of adenosine deaminase, beside the up-regulated expression of  CD39, could underlies an increased accumulation of extracellular ADO and its important role in Treg-mediated immune response suppression. Data of DLBCL, resembling the relapsed, tend to differentiate from other entities for a more suppressive functional profile. Together, these simple and fast assays obtained by FC support the finding that ATP-ectonucleotidase-adenosine system may have a role in mediating  Treg activity also  in lymphomas suggesting that  CD39 represents a possible target  for cancer immunotherapy.



Session topic: E-poster

Keyword(s): Lymphoma, Microenvironment, T regulatory cells

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