This article is part of the supplement: Association for Immunotherapy of Cancer: Cancer Immunotherapy – 2nd Annual Meeting .

Oral presentation

High frequency of functionally active Melan-A specific T cells in a patient with progressive immunoproteasome-deficient melanoma

N Meidenbauer¹, A Zippelius², MJ Pittet², M Laumer¹, S Vogl¹, J Heymann¹, M Rehli¹, B Seliger³, S Schwarz⁴, F-A Le Gal⁵, PY Dietrich⁵, R Andreesen¹, P Romero² and A Mackensen¹

¹  Department of Hematology/Oncology, University of Regensburg, Regensburg, Germany

²  Division of Clinical Onco-Immunology, Ludwig Institute for Cancer Research, University Hospital (CHUV), Lausanne, Switzerland

³  Johannes Gutenberg University, III. Department of Internal Medicine, Mainz, Germany

⁴  Department of Pathology, University of Regensburg, Regensburg, Germany

⁵  Laboratory of Tumor Immunology, Division of Oncology, University Hospital of Geneva, Geneva, Switzerland

author email corresponding author email

from Association for Immunotherapy of Cancer: Cancer Immunotherapy – 2^nd Annual Meeting
Mainz, Germany. 6–7 May 2004

Cancer Cell International 2004, 4(Suppl 1):S9doi:10.1186/1475-2867-4-S1-S9

The electronic version of this abstract is the complete one and can be found online at: http://www.cancerci.com/content/4/S1/S9

Received:	28 April 2004
Published:	1 July 2004

Oral presentation

Tumor-reactive T cells play an important role in cancer immuno-surveillance. Applying the multimer technology, we report here an unexpected high frequency of Melan-A-specific CTL in a melanoma patient with progressive lymph node (LN) metastases, consisting of 18% and 12.8% of total peripheral blood and tumor-infiltrating CD8⁺ T cells, respectively. Melan-A-specific CTL revealed a high cytotoxic activity against allogeneic Melan-A-expressing target cells but failed to kill the autologous tumor cells. Loading of the tumor cells with Melan-A peptide reversed the resistance to killing, suggesting impaired function of the MHC class I Ag processing and presentation pathway. Mutations and/or down-regulation of the MHC class I heavy chain, the antigenic peptide TAP, and tapasin could be excluded. However, RT-PCR and immunohistochemical analysis revealed a deficiency of the immunoproteasomes low molecular weight protein (LMP)2 and LMP7 in the primary tumor cells, that affects the quantity and quality of generated T cell epitopes and might explain the resistance to killing. Overall, this is the first report of an extremely high frequency of tumor-specific CTL that exhibit competent T cell effector functions, but fail to lyse the autologous tumor cells. Immunotherapeutic approaches should not only focus on the induction of a robust anti-tumor immune response, but also have to target tumor immune escape mechanisms.

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