Restoration of tumor-specific HLA class I restricted cytotoxicity in tumor infiltrating lymphocytes of advanced breast cancer patients by in vitro stimulation with tumor antigen-pulsed autologous dendritic cells.

Kass, Rena;Bellone, Stefania;Palmieri, Michela;Cané, Stefania;Santin, Alessandro D;et.al.
(2003) Breast Cancer Research and Treatment — Vol. 80, n° 3, p. 275-285 (2003)

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Authors
  • Kass, Rena
    Author
  • Bellone, Stefania
    Author
  • Palmieri, Michela
    Author
  • Cané, StefaniaUCLouvain
    Author
  • Santin, Alessandro D
    Author
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Abstract
Breast tumor infiltrating lymphocytes (TIL) are enriched in tumor-specific cytotoxic T lymphocytes (CTL), and may represent a superior source of CTL compare to peripheral blood lymphocytes (PBL), for adoptive T cell immunotherapy of breast cancer. However, the immunocompetence of TIL and the possibility to consistently restore their tumor-specific lytic activity in vitro remains an open issue. In this study we evaluated the potential of tumor antigen-pulsed fully mature dendritic cell (DC) stimulation in restoring tumor-specific cytotoxicity in anergic TIL populations from advanced breast cancer patients. In addition we have compared tumor-specific T cell responses induced by tumor antigen-loaded DC stimulation of TIL to responses induced from PBL. Although TIL were consistently non-cytotoxic after isolation or culture in the presence of interleukin-2 (IL-2), in matched experiments from three consecutive patients, tumor-lysate-pulsed DC-stimulated CD8+ T cell derived from TIL were found to be significantly more cytotoxic than PBL (p < 0.05). In addition, cytotoxicity against autologous tumor cells was more significantly inhibited by an anti-HLA class I (W6/32) MAb in TIL compared to PBL (p < 0.05). CTL populations derived from TIL and PBL did not lyse autologous EBV-transformed lymphoblastoid cell lines, and showed negligible cytotoxicity against the NK-sensitive cell line K562. Furthermore, in both CD8+ T cell populations the majority of the tumor-specific CTL exhibited a Th1 cytokine bias (IFN-gamma(high)/IL-4(low)). Taken together, these data show that tumor lysate-pulsed mature DC can consistently restore tumor-specific lytic activity in non-cytotoxic breast cancer TIL. These results may have important implications for the treatment of chemotherapy resistant breast cancer with active or adoptive immunotherapy.
Affiliations
  • University of Arkansas for Medical SciencesDivision of Gynecologic Oncology

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Kass, R., Bellone, S., Palmieri, M., Cané, S., Bignotti, E., Henry-Tillman, R., Hutchins, L., Cannon, M. J., Klimberg, S., & Santin, A. D. (2003). Restoration of tumor-specific HLA class I restricted cytotoxicity in tumor infiltrating lymphocytes of advanced breast cancer patients by in vitro stimulation with tumor antigen-pulsed autologous dendritic cells. Breast Cancer Research and Treatment, 80(3), 275-285. https://doi.org/10.1023/A:1024938215782 (Original work published 2003)