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TREG CD4 PHENOTYPE IN THE PERIPHERAL BLOOD OF LYMPHOMAS
Author(s): ,
Rosa Di Gaetano
Affiliations:
Haematology Castelfranco Veneto,Azienda ULSS 2 Marca Trevigiana,Castelfranco Veneto ( TV ),Italy
,
Donata Belvini
Affiliations:
Haematology Castelfranco Veneto,Azienda ULSS 2 Marca Trevigiana,Castelfranco Veneto ( TV ),Italy
,
Elena Pilotto
Affiliations:
Haematology Castelfranco Veneto,Azienda ULSS 2 Marca Trevigiana,Castelfranco Veneto ( TV ),Italy
,
Barbara Callegari
Affiliations:
Haematology Castelfranco Veneto,Azienda ULSS 2 Marca Trevigiana,Castelfranco Veneto ( TV ),Italy
,
Maria Angela De Benedetto
Affiliations:
Haematology Castelfranco Veneto,Azienda ULSS 2 Marca Trevigiana,Castelfranco Veneto ( TV ),Italy
,
Roberto Sartori
Affiliations:
Haematology Castelfranco Veneto,Azienda ULSS 2 Marca Trevigiana,Castelfranco Veneto ( TV ),Italy
Giuseppe Tagariello
Affiliations:
Haematology Castelfranco Veneto,Azienda ULSS 2 Marca Trevigiana,Castelfranco Veneto ( TV ),Italy
(Abstract release date: 05/18/17) EHA Library. Di Gaetano R. 05/18/17; 182791; PB2077
Dr. Rosa Di Gaetano
Dr. Rosa Di Gaetano
Contributions
Abstract

Abstract: PB2077

Type: Publication Only

Background

The T regulatory (Treg) cells down-regulate antitumor responses by several distinct mechanisms. One is the adenosinergic pathway which, through ectonucleotidases, sequentially converts ATP to AMP and generates immunosuppressive adenosine. Several studies have demonstrated in humans the overexpression of CD39 (NTPDase) and low adenosine deaminase (ADA) levels, the enzyme responsible for adenosine breakdown, and of CD26, a surface-bound ADA associated glycoprotein. In our previous work (Di Gaetano et al, Ann Haematol, 2014) we analysed by flow cytometry (FC) the T CD4 lymphocytes of solid biopsies, the surrounding neoplastic cells in Hodgkin lymphoma (HL) lymph nodes (LN) and we demonstrated the presence of an activated profile (CD38+) with a reduction of CD26 (CD4+CD26-CD38+). We also confirmed a link of this subset with an overexpression of CD39.

Aims

By using the same FC technique we wanted to explore if, as in the lymph nodes, CD4+CD26-CD38+ subset and high levels of CD39 might characterize the peripheral blood (PB) of HL at diagnosis and possibly to distinguish them from those of B Non-Hodgkin lymphomas (B-NHL).

Methods

We have analysed by FC the PB of 16 healthy controls (HC), 10 HL and 22 NHL testing within T CD4 cells the expression of CD26, CD38 and CD39.

Results
In HC CD26-CD38+ cells were 2.6% of all T CD4 and 5.5% expressed CD39. Compared with HC, the subset CD4+CD26-CD38+ of HL was statistically different (2.6 vs 17; p < 0.05) as well as in B-NHL (2.6 vs 12.9; p < 0.05). The expression of CD39 between HC and HL was not different (5 vs 9.8; p = 0.1), while it was statistically significant between HC and NHL (5 vs 19.5; p < 0.05).

Conclusion

Our results may suggest that T CD4 profile in the PB can characterize the patients with HL and B-NHL and this could be probably variable according to the type of neoplasm. The significant presence of CD4+CD26-CD38+ subset in PB of HL and B-NHL would seem to suggest that the low expression/reduction of CD26 of ADA activity may indicate the Treg-mediated immunosuppression. Interesting is the diversity of NHL showing increased CD39 expression on T CD4 lymphocytes probably connected with the clone of B lymphocytes involved in cancer. This may support that leukemic cells may contribute to create and to characterize an immune-subversive environment and to facilitate immune escape mechanisms. FC analysis of CD26 and CD39, markers likely connected with the adenosinergic pathway, in PB can represent effective parameters to determine and characterize the Treg CD4 in different types of lymphoma and could serve as targets in the follow-up of HL and B-NHL.

Session topic: 18. Non-Hodgkin & Hodgkin lymphoma - Biology

Keyword(s): T regulatory cells, Peripheral blood, lymphoma, Cytometry

Abstract: PB2077

Type: Publication Only

Background

The T regulatory (Treg) cells down-regulate antitumor responses by several distinct mechanisms. One is the adenosinergic pathway which, through ectonucleotidases, sequentially converts ATP to AMP and generates immunosuppressive adenosine. Several studies have demonstrated in humans the overexpression of CD39 (NTPDase) and low adenosine deaminase (ADA) levels, the enzyme responsible for adenosine breakdown, and of CD26, a surface-bound ADA associated glycoprotein. In our previous work (Di Gaetano et al, Ann Haematol, 2014) we analysed by flow cytometry (FC) the T CD4 lymphocytes of solid biopsies, the surrounding neoplastic cells in Hodgkin lymphoma (HL) lymph nodes (LN) and we demonstrated the presence of an activated profile (CD38+) with a reduction of CD26 (CD4+CD26-CD38+). We also confirmed a link of this subset with an overexpression of CD39.

Aims

By using the same FC technique we wanted to explore if, as in the lymph nodes, CD4+CD26-CD38+ subset and high levels of CD39 might characterize the peripheral blood (PB) of HL at diagnosis and possibly to distinguish them from those of B Non-Hodgkin lymphomas (B-NHL).

Methods

We have analysed by FC the PB of 16 healthy controls (HC), 10 HL and 22 NHL testing within T CD4 cells the expression of CD26, CD38 and CD39.

Results
In HC CD26-CD38+ cells were 2.6% of all T CD4 and 5.5% expressed CD39. Compared with HC, the subset CD4+CD26-CD38+ of HL was statistically different (2.6 vs 17; p < 0.05) as well as in B-NHL (2.6 vs 12.9; p < 0.05). The expression of CD39 between HC and HL was not different (5 vs 9.8; p = 0.1), while it was statistically significant between HC and NHL (5 vs 19.5; p < 0.05).

Conclusion

Our results may suggest that T CD4 profile in the PB can characterize the patients with HL and B-NHL and this could be probably variable according to the type of neoplasm. The significant presence of CD4+CD26-CD38+ subset in PB of HL and B-NHL would seem to suggest that the low expression/reduction of CD26 of ADA activity may indicate the Treg-mediated immunosuppression. Interesting is the diversity of NHL showing increased CD39 expression on T CD4 lymphocytes probably connected with the clone of B lymphocytes involved in cancer. This may support that leukemic cells may contribute to create and to characterize an immune-subversive environment and to facilitate immune escape mechanisms. FC analysis of CD26 and CD39, markers likely connected with the adenosinergic pathway, in PB can represent effective parameters to determine and characterize the Treg CD4 in different types of lymphoma and could serve as targets in the follow-up of HL and B-NHL.

Session topic: 18. Non-Hodgkin & Hodgkin lymphoma - Biology

Keyword(s): T regulatory cells, Peripheral blood, lymphoma, Cytometry

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