One possible reason for the poor immunogenicity of
tumors is the induction of peripheral tolerance by
tumor cells that fail to deliver costimulatory signals. Furthermore, T cells stimulated with wild-type
tumor cells often fail to secrete
cytokines. The present study has been undertaken to identify
cytokines that cooperate with CD80 in T-cell activation in vitro toward human breast and ovarian
carcinoma cell lines.
Tumor cell-mediated T-lymphocyte activation was analyzed directly in allogeneic mixed lymphocyte/
tumor cell cultures as proliferation and effector functions were assessed in cytotoxic T-cell assays.
Interleukin-7 (IL-7) amplified the proliferative response toward CD80-transfected breast and ovarian
carcinomas and stimulated predominantly CD4+ T lymphocytes.
IL-12 represses the proliferative response of naive T cells but cooperates with CD80-mediated activation during secondary stimulations. In long-term T-cell cultures,
IL-12 synergizes with CD80 expression to stimulate cytolytic CD8+ T-cell lines, which recognize a
breast carcinoma line in a human histocompatibility leukocyte
antigen-restricted manner. These studies illustrate that costimulation is necessary for
tumor cells to function as
alloantigen-presenting cells. Furthermore, when added after the priming of T cells with CD80-transfected
tumor cells,
IL-12 could be helpful in propagating sufficient T-cell numbers to be used in adoptive transfers during cellular
immunotherapy.