TREG DOWNREGULATION IS ASSOCIATED WITH INCREASE OF T CELL RESPONSES AGAINST IMMUNOGENIC ANTIGENS AND CLINICAL RESPONSES IN PATIENTS WITH HEMATOLOGICAL MALIGNANCIES AFTER DONOR LYMPHOCYTE INFUSION
Author(s): ,
Jochen Greiner
Affiliations:
Department of Internal Medicine,Diakonie Hospital,Stuttgart,Germany;Clinic for Internal Medicine III,University of Ulm,Ulm,Germany
,
Marlies Götz
Affiliations:
Clinic for Internal Medicine III,University of Ulm,Ulm,Germany
,
Michael Schmitt
Affiliations:
Clinic for Internal Medicine V,University of Heidelberg,Heidelberg,Germany
,
Markus Wiesneth
Affiliations:
Institute of Transfusion Medicine,University of Ulm and German Red Cross,Ulm,Germany
,
Donald Bunjes
Affiliations:
Clinic for Internal Medicine III,University of Ulm,Ulm,Germany
Susanne Hofmann
Affiliations:
Clinic for Internal Medicine V,University of Heidelberg,Heidelberg,Germany
EHA Library. GREINER J. Jun 14, 2019; 266582; PF783
Prof. Dr. Jochen GREINER
Prof. Dr. Jochen GREINER
Contributions
Abstract

Abstract: PF783

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background

Cytotoxic T-cell responses against malignant cells play a pivotal role in maintaining remission and prolonging overall-survival after allogeneic stem cell transplantation (allo-SCT) and donor lymphocyte infusion (DLI), however they are not well characterized so far.

Aims

In this study, we focused on the detection of immune responses in patients before and after DLI. A broader epitope-specific T cell activity is associated with clinical response of patients treated with DLI and additionally reduced regulatory T cell frequency may contribute to clinical response in patients after DLI.

Methods

For a better characterization of the T cell responses, frequency and diversity of leukemia-associated antigen (LAA)-specific cytotoxic T cells was assessed using ELISpot and pMHC multimer assays. Furthermore, the frequency of regulatory T cells (Treg) before and after DLI was analyzed. Results were correlated to the clinical course of the patients.

Results

Independently of their clinical response, over the course of DLI 7/11 patients (63.6%) showed an immunological response through an increase in the number of recognized epitopes. Comparing early screening and maximum response after DLI there was a significant increase (p=0.02) in epitope recognition. A significant increase in the mean augmentation from 1 to 4 of the spotted epitopes in the course of DLI was detected in the cohort of clinical responders (R) compared to non-responders (NR) who did not show any dynamics in epitope recognition with a median of 3 to 4 recognized LAA.

The proportion of the CD4+CD25highFoxP3+ Treg within the CD4+CD25high T cell fraction decreased significantly in R from a median of 72.9% to 54.6% when comparing the variation at the time points before and after DLI (p=0.04). In NR there was no significant change in the Treg fraction in the course of DLI.

In general, significantly more LAA-derived T cell epitopes (p=0.02) were recognized in R when compared to NR. Moreover, the frequency of Treg in R decreased significantly (p=0.008) while remaining stable in NR.

Conclusion

Taken together, an increase of specific CTL responses against several LAA after DLI was detected. This study suggests that decreasing numbers of Treg as well as enhanced LAA diversity in T cell responses contribute to clinical outcome of patients treated with DLI.

Session topic: 21. Stem cell transplantation - Experimental

Keyword(s): Cytotoxic T cell, Donor lymphocyte infusion, Regulatory T cell

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