In vitro immunization of patient T cells with autologous bone marrow antigen presenting cells pulsed with tumor lysates

Int J Cancer. 2000 Dec 1;88(5):783-90. doi: 10.1002/1097-0215(20001201)88:5<783::aid-ijc16>3.0.co;2-m.

Abstract

Presentation of cell-associated antigen to T cells is a critical event in the initiation of an anti-tumor immune response but it appears to often be deficient or limiting. Here we report an experimental system for stimulation of human T lymphocytes using autologous antigen presenting cells (APCs) and autologous tumor cells. Two types of APCs were prepared from human bone marrow: MC and DC. MC were produced by using GM-CSF and SCF. DC were obtained with the same cytokines plus IL-4. DC and MC were generated in parallel from the same patients and their phenotypes and capacities to prime T lymphocytes were analyzed and compared. MC were CD14+, CD1a-, CD33+ and HLA-DR+. Two populations of DC were defined: immature DC were uniformly CD1a-; mature DC expressed CD1a, CD80, CD86, HLA-DR, CD54 and CD58 but lacked surface CD14. Stimulation of autologous T lymphocytes was studied by measuring their proliferation and cytotoxic function. In more than 80% of our experiments the proliferation of autologous T lymphocytes cocultured with APC pulsed or not with tumor cell lysates was higher than that of T cells cultured alone. DC were more effective than MC in stimulating proliferation of lymphocytes. The capacity of a patient's autologous bone marrow-derived APC to stimulate T cells when exposed to autologous tumor cell lysates suggest that such antigen-exposed APC may be useful in specific anti-tumor immunotherapy protocols.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen-Presenting Cells / immunology*
  • Antigens, Neoplasm / immunology
  • Antigens, Surface / immunology
  • Autoantigens / immunology
  • Bone Marrow / immunology*
  • Bone Marrow / metabolism
  • Coculture Techniques
  • Cytotoxicity, Immunologic
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Humans
  • Immunophenotyping
  • Kidney Neoplasms / immunology*
  • Kidney Neoplasms / pathology
  • Lymphocyte Activation / immunology*
  • Macrophages / immunology
  • Melanoma / immunology*
  • Melanoma / pathology
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • T-Lymphocytes, Cytotoxic / immunology
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antigens, Neoplasm
  • Antigens, Surface
  • Autoantigens
  • Tumor Necrosis Factor-alpha