Different cytokine profiles released by CD4+ and CD8+ tumor-draining lymph node cells involved in mediating tumor regression

Abstract

Abstract:We have previously demonstrated that the growth of weakly immunogenic murine sarcomas leads to

Enhanced signaling through the IL-2 receptor in CD8+T cells regulated by antigen recognition results in preferential proliferation and expansion of responding CD8+T cells rather than promotion of cell death

“…CD8 ϩ T cells generally lose the ability to produce IL-2 after differentiation into effector T cells (17,18). Based on the two opposing effects of IL-2R signaling, this might not only result in tighter regulation of the CD8 ϩ T cell response by increasing the dependence for continued expansion on CD4 ϩ T helper (Th) cell production of IL-2, but also represent a mechanism to shield CD8 ϩ T cells from IL-2-mediated cell death.…”

Tumor-Specific Responses in Lymph Nodes Draining Murine Sarcomas Are Concentrated in Cells Expressing P-Selectin Binding Sites

“…Tumor-specific cytokine production in vitro was measured by coculture of irradiated tumor cells with cultured TDLN fractions, as described (4,10). In brief, 1 ϫ 10 6 freshly disaggregated and irradiated MCA 205 or 207 tumor cells were combined with equal numbers of cultured TDLN cells in 2 ml MLM containing 60 IU human rIL-2.…”

“…infusion of cultured TDLN cells 3 days after infusion of tumor cells. Eleven to eighteen days later, the mice were sacrificed and examined for pulmonary metastases, as described (4,10). ANOVA with multiple comparisons (Tukey test) was used to determine whether the mean numbers of pulmonary metastases under different treatment conditions were significantly different.…”

“…One approach uses tumor-draining lymph nodes (TDLN) 4 as a source for tumor-responsive pre-effector cells (2,3). Activation of murine TDLN on immobilized ␣CD3 and growth in low-dose IL-2 produced T lymphoblasts showing strain-specific antitumor activities in vitro and in vivo.…”

“…These lymphoblasts secreted IFN-␥ when cocultured with syngeneic tumor, and suppressed the growth of established pulmonary micrometastases following i.v. infusion (4). In a small phase I clinical trial, T cells cultured from lymph nodes primed with autologous tumor-derived vaccines showed tumor-specific IFN-␥ secretion in vitro and produced measurable tumor regression following adoptive transfer in 33% of patients with disseminated renal cell carcinomas (2 complete and 2 partial responses among 12 participants) (5).…”