Induction of tumour-specific CD8 cytotoxic T lymphocytes by tumour lysate-pulsed autologous dendritic cells in patients with uterine serous papillary cancer

• Published in: British journal of cancer 2002-01, Vol.86 (1), p.151-157
• Main Authors: Santin, A D, Bellone, S, Ravaggi, A, Roman, J J, Pecorelli, S, Parham, G P, Cannon, M J
• Format: Article
• Language: English
• Subjects: Antigens; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Carcinoma, Papillary - immunology; Chemotherapy; Cytokines; Cytokines - biosynthesis; Cytotoxicity; Dendritic cells; Dendritic Cells - immunology; Drug Resistance; Endometrial cancer; Endometrial Neoplasms - immunology; Epidemiology; Experimental Therapeutics; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; Histocompatibility Testing; Humans; Immunophenotyping; Immunotherapy; Lymphocytes; Medical prognosis; Medical research; Medical sciences; Middle Aged; Molecular Medicine; Oncology; Ovarian cancer; Patients; Peptides; T-Lymphocytes, Cytotoxic - immunology; Tumor Cells, Cultured; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600026

Uterine serous papillary carcinoma is a highly aggressive variant of endometrial cancer histologically similar to high grade ovarian cancer. Unlike ovarian cancer, however, it is a chemoresistant disease from onset, with responses to combined cisplatinum-based chemotherapy in the order of 20% and an extremely poor prognosis. In this study, we demonstrate that tumour lysate-pulsed autologous dendritic cells can elicit a specific CD8 + cytotoxic T lymphocyte response against autologous tumour target cells in three patients with uterine serous papillary cancer. CTL from patients 1 and 2 expressed strong cytolytic activity against autologous tumour cells, did not lyse autologous lymphoblasts or autologous EBV-transformed cell lines, and were variably cytotoxic against the NK-sensitive cell line K-562. Patient 3 CD8 + T cells expressed a modest but reproducible cytotoxicity against autologous tumour cells only at the time of the first priming. Further priming attempts with PBL collected from patient 3 after tumour progression in the lumboaortic lymph nodes were unsuccesful. Cytotoxicity against autologous tumour cells could be significantly inhibited by anti-HLA class I (W6/32) and anti-LFA-1 MAbs. Highly cytotoxic CD8 + T cells from patients 1 and 2 showed a heterogeneous CD56 expression while CD56 was not expressed by non-cytotoxic CD8 + T cells from patient 3. Using two colour flow cytometric analysis of intracellular cytokine expression at the single cell level, a striking dominance of IFN-γ expressors was detectable in CTL populations of patients 1 and 2 while in patient 3 a dominant population of CD8 + T cells expressing IL-4 and IL-10 was consistently detected. Taken together, these data demonstrate that tumour lysate-pulsed DC can be an effective tool in inducing uterine serous papillary cancer-specific CD8 + CTL able to kill autologous tumour cells in vitro . However, high levels of tumour specific tolerance in some patients may impose a significant barrier to therapeutic vaccination. These results may have important implications for the treatment in the adjuvant setting of uterine serous papillary cancer patients with active or adoptive immunotherapy.