DARWIN Digitale Dissertationen German Version Strich

FU Berlin
Digitale Dissertation

Anne Letsch :
High frequencies of circulating Melanoma-reactive CD8+ T Cells in patients with advanced melanoma
Nachweis hoher Frequenzen zirkulierender Melanom-reaktiver CD8+ T-Zellen bei Patienten mit fortgeschrittenem Melanom

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Abstract

To determine whether circulating tumor-reactive T cells are present in melanoma patients, unstimulated T cells from peripheral blood were tested for recognition of HLA-A2- or HLA?A1-matched melanoma cell lines using the ELISPOT assay. Eleven out of nineteen patients with metastatic melanoma had a T cell response with up to 0.81%, 0.78%, 0.53%, 0.12%, 0.10%, 0.09%, 0.07%, 0.06%, 0.06%, 0.04% and 0.04% of peripheral blood mononuclear cells (PBMC) secreting IFN gamma upon exposure to various HLA-A2- or HLA-A1-matched melanoma cell lines. These T cell responses were mediated by CD8+ T cells and could specifically be blocked by an anti-HLA-A2 antibody in HLA-A2-positive patients. Separation experiments performed in one melanoma patient showed tumor-reactive T cells in both the CD8+ effector T cell (CD45RA+/IFN gamma+) as well as the CD8+ memory T cell compartment (CD45RO+/IFN gamma+). In 3 out of 5 patients, in whom autologous cell lines were available, similar frequencies of T cells in response to HLA-A1- or HLA-A2-matched allogeneic and autologous tumor cells were observed, while 2 patients had a T cell response restricted to either the autologous or the allogeneic cell lines. These results give evidence for the presence of tumor-reactive CD8+ T cells in more than half of melanoma patients tested. Although some of these patients have clinical evidence for an immunological mediated tumor control several patients have growing tumors suggesting presence of escape mechanisms.

Table of Contents

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0. Titelblatt und Inhaltsverzeichnis

1. Einleitung

2. Material und Methoden

3. Ergebnisse

4. Diskussion

5. Zusammenfassung

6. Literaturverzeichnis

More Information:

Online available: http://www.diss.fu-berlin.de/2002/72/indexe.html
Language of PhDThesis: german
Keywords: Melanoma, T cells, Tumorreactive T cells, ELISPOT
DNB-Sachgruppe: 33 Medizin
Date of disputation: 15-Jan-2002
PhDThesis from: Fachbereich Humanmedizin, Freie Universität Berlin
First Referee: PD Dr. Carmen Scheibenbogen
Second Referee: Prof. Dr. Dr. Christoph Geilen
Contact (Author): anne.letsch@medizin.fu-berlin.de
Contact (Advisor): carmen.scheibenbogen@medizin.fu-berlin.de
Date created:08-May-2002
Date available:15-May-2002

 

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