Volume 4 Supplement 1

Association for Immunotherapy of Cancer: Cancer Immunotherapy – 2ndAnnual Meeting

Open Access

Enrichment of functional CD8 memory T cells specific for MUC1 in Bone Marrow of Multiple Myeloma Patients

  • M Witzens1Email author,
  • C Choi2,
  • M Bucur2,
  • M Feuerer3,
  • N Sommerfeldt2,
  • A Trojan4,
  • A Ho1,
  • V Schirrmacher2,
  • H Goldschmidt1 and
  • P Beckhove2
Cancer Cell International20044(Suppl 1):S30

DOI: 10.1186/1475-2867-4-S1-S30

Received: 28 April 2004

Published: 1 July 2004

Objective

Recently, the bone marrow was shown to be a site were T cells are primed against blood borne antigens and tumor associated antigens. The common tumor-associated antigen (TAA) MUC1 has been shown to be expressed on about 90% of malignant plasma cells in multiple myeloma (MM). This study was performed to investigate the content and reactivity of MUC-1 specific memory T cells in BM compared to PB from MM patients with respect to possible use in immunotherapeutic strategies.

Methods

Paired BM and PB samples from 42 HLA-A2 pos. MM patients and 11 HLA-A2 pos. normal donors were tested for frequency of TAA-specific CD8 T cells by HLA-A2 tetramer-analysis using MUC1 derived peptide LLLTVLTV (12–20) as TAA or for frequency of tumor-reactive CD8 memory T cells in 40 h short term IFNy ELISPOT assay. Antigen specific cytotoxic potential of 6 patients T cells was evaluated by Chr51 chromium release assay following single restimulation with MUC1 peptide pulsed DCs. Presence of MUC1 expressing cells and CD8 T cells in BM biopsies from MM patients was detected by immunohistochemistry.

Results

The frequencies of MUC1-specific CD8 T cells in PB and BM of 42 tested patients varied between 0–6.4% of CD8 T cells. In contrast, PB and BM of 11 normal donors contained only 0–0.25% tetramer binding CD8 T cells. Enrichment of MUC1 specific CD8 T cells (> 0.3% of CD8 T cells) was found in PB and BM from 16 out of 30 patients (53%).

Using short term IFNγ ELISPOT functional-assay we detected enrichment of MUC1-reacticve CD8 memory T cells in BM from 6 out of 12 patients (50%). In contrast, in corresponding PB, MUC1-reactive T cells were detected in only 1 out of 9 patients (11%). The frequencies of MUC1-reactive CD8 memory T cells varied between 1:390–1:3350 (BM) and 1:3340 (PB). BMTCs from MM patients were able to kill MUC1-peptide loaded Target cells in a dose dependent manner in contrast to corresponding PB T cells from the same patients. CD8 T cells were co-localized together with MUC1 expressing cells in the BM of MM patients.

Conclusions

MUC1 specific T cells are highly enriched in PB and BM of about 50% of MM patients indicating induction and maintainance of tumor cell directed immune responses during the course of disease. We detected high amounts of MUC1-derived peptide specific CD8 memory T cells capable of IFNγ secretion and cytotoxicity upon appropriate restimulation in BM but not PB of MM patients. Thus, autologous BM-derived memory T cells reactivated in vitro with MUC1 pulsed dendritic cells might be useful for future immunotherapy of MM.

Authors’ Affiliations

(1)
Department of Hematology and Oncology, The University Hospital Heidelberg
(2)
Tumor Immunology Program, The German Cancer Research Center
(3)
Department of Experimental Rheumatology, Medical Clinic, Charité, Humboldt University
(4)
Department of Oncology, University Hospital Zurich

Copyright

© Author(s); licensee BioMed Central Ltd. 2004

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