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IMPACT OF TREATMENT ON RNA EXPRESSION OF IMMUNE PROFILE IN PATIENTS WITH CLASSICAL HODGKIN LYMPHOMA
Author(s): ,
Priscilla Silva
Affiliations:
Clinical Oncology and Experimental,Federal University of São Paulo,Sao Paulo,Brazil
,
Juliana Monte Real
Affiliations:
Clinical Oncology and Experimental,Federal University of São Paulo,Sao Paulo,Brazil
,
Ludmila Ferreira
Affiliations:
Lab. Immunology, Heart Institute,University of São Paulo School of Medicine,Sao Paulo,Brazil
,
Gustavo Esteves
Affiliations:
Estatistic,University of Paraiba State,Campina Grande,Brazil
,
Joao Garibaldi Jr
Affiliations:
Clinical Oncology and Experimental,Federal University of São Paulo,Sao Paulo,Brazil
,
Fabio Brito
Affiliations:
Clinical Oncology and Experimental,Federal University of São Paulo,Sao Paulo,Brazil
,
Adriana Penna
Affiliations:
Clinical Oncology and Experimental,Federal University of São Paulo,Sao Paulo,Brazil
,
Egyla Cavalcante
Affiliations:
Clinical Oncology and Experimental,Federal University of São Paulo,Sao Paulo,Brazil
Otavio Baiocchi
Affiliations:
Clinical Oncology and Experimental,Federal University of São Paulo,Sao Paulo,Brazil
(Abstract release date: 05/19/16) EHA Library. Baiocchi O. 06/09/16; 132944; E1395
Prof. Dr. O Baiocchi
Prof. Dr. O Baiocchi
Contributions
Abstract
Abstract: E1395

Type: Eposter Presentation

Background
Although immunosuppression has long been recognized in classical Hodgkin lymphoma (cHL), the underlying basis for the lack of an effective immune response against tumor remains unclear. Recently, our group showed increased frequencies of pro and anti-inflammatory cytokines, such as interleukins (IL)-6, IL-10, TNF-alpha and sCD25, in cHL patients and the impact of treatment on these cytokines. These cytokines participate in the Hodgkin and Reed-Sternberg (HRS) cells survival and immunological escape.

Aims
In this study we aimed to evaluate the immune gene expression profile in cHL patients at diagnosis and the impact of treatment on this profile.

Methods
Twenty consecutively diagnosed cHL patients, with whole blood RNA extracted at diagnosis and after treatment, were recruited for this study and prospectively evaluated. The general expression of 96 messengers RNAs present in the peripheral blood and involved in immune response was performed by a customized quantitative real-time PCR array (TaqMan® Low Density Array). We also included 7 healthy controls. The data was normalized with B2M mRNAs levels and relative gene expression was calculated by the 2^DDCt method, considering Wilcoxon test and Benjamini-Hochberg adjustment to correct p-values.

Results
At diagnosis we observed that blood of cHL patients presents higher expression of IL-10 (2.4 fold, p=0.013) and decreased expression of CCL2 (-5 fold, p=0.028), CD40 (-2 fold, p=0.013) and HLA-DRA (-2 fold, p=0.028) compared with healthy controls. On the other hand, after treatment, the mRNAs levels returned to normal and no immune-related gene studied was found in different amounts when compared to control subjects. Considering patients after treatment, an important reduced expression of BCL2 (1.5 fold, p= 0.043), CCL2 (3,7 fold, p= 0.003); CCL22 (1.9 fold, p=0.025); CCL5 (1.7 fold, p=0.025), CD40 (2.2 fold, p=0.007), CD80 (2 fold, p=0.015), CSF2(2,5 fold, p=0.007), HLA-DRA (1.7 fold, p=0.025), IL-2RA (1.7 fold, p=0.025), IL-4 (2.5 fold, p=0.007), IL-6 (3.7 fold, p=0.007), LTA(1.7 fold, p=0.038), RORC (1.6 fold, p=0.025) in comparison with cHL patients before treatment. Epidemiologic and clinical correlation are currently being done.

Conclusion
In this study, we showed that, at diagnosis, cHL patients presented with more inflammatory gene expression and, after treatment, a more effector immunological profile is found. Interestingly, posttreatment immunological profile is similar to healthy controls. Understanding cHL associated immunosuppression and the immune reconstitution after treatment maybe the key to develop new prognostic factors and treatment strategies.



Session topic: E-poster

Keyword(s): Gene expression profile, Hodgkin's lymphoma, Immune response, Treatment
Abstract: E1395

Type: Eposter Presentation

Background
Although immunosuppression has long been recognized in classical Hodgkin lymphoma (cHL), the underlying basis for the lack of an effective immune response against tumor remains unclear. Recently, our group showed increased frequencies of pro and anti-inflammatory cytokines, such as interleukins (IL)-6, IL-10, TNF-alpha and sCD25, in cHL patients and the impact of treatment on these cytokines. These cytokines participate in the Hodgkin and Reed-Sternberg (HRS) cells survival and immunological escape.

Aims
In this study we aimed to evaluate the immune gene expression profile in cHL patients at diagnosis and the impact of treatment on this profile.

Methods
Twenty consecutively diagnosed cHL patients, with whole blood RNA extracted at diagnosis and after treatment, were recruited for this study and prospectively evaluated. The general expression of 96 messengers RNAs present in the peripheral blood and involved in immune response was performed by a customized quantitative real-time PCR array (TaqMan® Low Density Array). We also included 7 healthy controls. The data was normalized with B2M mRNAs levels and relative gene expression was calculated by the 2^DDCt method, considering Wilcoxon test and Benjamini-Hochberg adjustment to correct p-values.

Results
At diagnosis we observed that blood of cHL patients presents higher expression of IL-10 (2.4 fold, p=0.013) and decreased expression of CCL2 (-5 fold, p=0.028), CD40 (-2 fold, p=0.013) and HLA-DRA (-2 fold, p=0.028) compared with healthy controls. On the other hand, after treatment, the mRNAs levels returned to normal and no immune-related gene studied was found in different amounts when compared to control subjects. Considering patients after treatment, an important reduced expression of BCL2 (1.5 fold, p= 0.043), CCL2 (3,7 fold, p= 0.003); CCL22 (1.9 fold, p=0.025); CCL5 (1.7 fold, p=0.025), CD40 (2.2 fold, p=0.007), CD80 (2 fold, p=0.015), CSF2(2,5 fold, p=0.007), HLA-DRA (1.7 fold, p=0.025), IL-2RA (1.7 fold, p=0.025), IL-4 (2.5 fold, p=0.007), IL-6 (3.7 fold, p=0.007), LTA(1.7 fold, p=0.038), RORC (1.6 fold, p=0.025) in comparison with cHL patients before treatment. Epidemiologic and clinical correlation are currently being done.

Conclusion
In this study, we showed that, at diagnosis, cHL patients presented with more inflammatory gene expression and, after treatment, a more effector immunological profile is found. Interestingly, posttreatment immunological profile is similar to healthy controls. Understanding cHL associated immunosuppression and the immune reconstitution after treatment maybe the key to develop new prognostic factors and treatment strategies.



Session topic: E-poster

Keyword(s): Gene expression profile, Hodgkin's lymphoma, Immune response, Treatment

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