TUMOR IMMUNE ESCAPE MEDIATED BY TH17CCR4-CCR6+ CELLS AND IL-6/IL-10/IL-17A IN ACUTE MYELOID LEUKEMIA
Author(s): ,
Amaya Zabalza
Affiliations:
Hematology,Complejo Hospitalario de Navarra,Pamplona,Spain;Oncohematology Research Group,Navarrabiomed-Miguel Servet Foundation, Navarra’s Health Research Institute (IDISNA),Pamplona,Spain
,
Elena Soria
Affiliations:
Oncohematology Research Group,Navarrabiomed-Miguel Servet Foundation, Navarra’s Health Research Institute (IDISNA),Pamplona,Spain
,
Miren Vallejo
Affiliations:
Oncohematology Research Group,Navarrabiomed-Miguel Servet Foundation, Navarra’s Health Research Institute (IDISNA),Pamplona,Spain
,
Cristina Mansilla
Affiliations:
Oncohematology Research Group,Navarrabiomed-Miguel Servet Foundation, Navarra’s Health Research Institute (IDISNA),Pamplona,Spain
,
Monserrat Alvarellos
Affiliations:
Hematology,Complejo Hospitalario de Navarra,Pamplona,Spain
,
Patricia García-Ramirez
Affiliations:
Hematology,Complejo Hospitalario de Navarra,Pamplona,Spain
,
María Ángeles Ardaiz
Affiliations:
Hematology,Complejo Hospitalario de Navarra,Pamplona,Spain
,
María Carmen Mateos
Affiliations:
Hematology,Complejo Hospitalario de Navarra,Pamplona,Spain
Natalia Ramirez
Affiliations:
Oncohematology Research Group,Navarrabiomed-Miguel Servet Foundation, Navarra’s Health Research Institute (IDISNA),Pamplona,Spain
EHA Library. Zabalza A. Jun 15, 2019; 266635; PS1018
Dr. Amaya Zabalza
Dr. Amaya Zabalza
Contributions
Abstract

Abstract: PS1018

Type: Poster Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 17:30 - 19:00

Location: Poster area

Background
Acute myeloid leukemia (AML) is a hematologic neoplasm characterized by the proliferation of bone marrow myeloblasts. Most of patients achieve remission after intensive chemotherapy, although they still relapse. The immune system play an important role in the pathogenesis of AML, where myeloblasts are be able to switch the immunological synapsis disabling the generation of an anti-tumor response. In this sense, the presence of a greater number of Th17 lymphocytes has been described in AML.

Aims
To elucidate whether the myeloblats modulate the Th17 population and more specifically the two Th17 subpopulations: CCR4+ and CCR4-.

Methods
From February 2015 to March 2018, 20 AML diagnosed patients at the CHN and 20 controls were included. Blood samples were collected at diagnosis from AML patients and in controls.  We identified by flow cytometry the populations of T helper cells (Th1, Th2, Th17 CCR4-CCR6+, Th17 CCR4+CCR6+) with the following monoclonal antibodies: CD3 Horizon-V450, CCR3 FITC, IFNγRβ PE, CCR4 PE-Cy7, CD4 PerCP, CCR6 APC, CD45 APC-H7, CCR5 FITC, CXCR3 APC in a FACSCanto II. Serum level of cytokines were also analysed by CBA Human Th1/Th2/Th17 Cytokine Kit (BD) for IL-2, IL-4, IL-6, IL-10, TNFα, IFNγ, and IL-17A. We also study the polimorfism of IL-17A (rs2275913) and IL-17F (rs763780) by allele discrimination by real-time PCR. The SPSS software was used to perform Student´s test or Mann-Whitney test for unpaired samples between patients and controls, and simple linear regression was used to study the association between levels of cytokines and Th subpopulations in AML patients. P<0,05 was considered to be statistically significant.

Results
Patients and controls characteristics were showed in table 1. Th1 and Th2 cells levels did not differ between AML patients and controls. The mean of Th17 CCR4-CCR6+ cells was significantly higher in AML patients (192±178/μl) than those in controls (67±38/μl), and the difference was statistically significant (p=0,027). However, Th17 CCR4+CCR6+ cells levels did not differ between groups. We did not find significant differences in the levels of IL-2, IL-4, TNFα and IFNγ citokines. Th17 related cytokines were significantly higher in AML patients than in controls and statistically significant. The mean of cytokines (pg/ml) in AML and in controls was 32,79±86,64 vs 0 (p<0,01), 3,03±2,65 vs 0,24±0,52 (p<0,001), 14,37±14,12 vs 2,38±4,17 (p=0,012), for IL-6, IL-10 and IL-17A respectively. No association was find by simple linear regression between the levels of IL-6, IL-10 and IL-17A, and the Th17 subpopulations. There are also no significant differences between the polymorphisms studied of IL-17 in patients and controls.

Conclusion
Th17 subpopulations could play a role in the pathophysiology of AML. The most relevant subpopulation described is the Th17 CCR4+CCR6+. Protumoral and antitumor properties have been described for this subpopulation and associated cytokines (IL-6, IL-10 and IL-17A). However, our results show an increase in the levels of the Th17 CCR4-CCR6+ subpopulation and in IL-6, IL-10 and IL-17A in untreated AML patients. The lack of association between Th17 subpopulations and cytokines implies that AML generates a protumoral microenvironment, where Th17 subpopulation and associated cytokines are regardless regulated by the tumor. Specifically, the downregulation of CCR4 antigen expression prevents the cells from migrating and having an antitumor effect and the upregulation of IL-6, IL-10 and IL-17A secretion very likely from Th17 CCR4+CCR6+ could contribute to the progression of the disease.

Session topic: 3. Acute myeloid leukemia - Biology & Translational Research

Keyword(s): Acute myeloid leukemia, T lymphocyte, helper

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies