Tumor Rejection After Direct Costimulation of CD8 ⁺ T Cells by B7-Transfected Melanoma Cells

Abstract

A variety of tumors are potentially immunogenic but do not stimulate an effective anti-tumor immune response in vivo. Tumors may be capable of delivering antigen-specific signals to T cells, but may not deliver the costimulatory signals necessary for full activation of T cells. Expression of the costimulatory ligand B7 on melanoma cells was found to induce the rejection of a murine melanoma in vivo. This rejection was mediated by CD8+ T cells; CD4+ T cells were not required. These results suggest that B7 expression renders tumor cells capable of effective antigen presentation, leading to their eradication in vivo.

Tumor cells expressing membrane-bound form of IL-4 induce antitumor immunity

“…38 Induction of anergy is prevented by providing IL-2 or crosslinking the IL-2 receptor, 39,40 and tumors with appropriate costimulation such as CD80 or CD86 effectively induce an antitumor immune response. 41 The TAA peptides associated with MHC class I and the IL4m molecules on tumor cells were expected to function as signal 1 and 2, respectively. This mode of T cell activation may lead to specific activation of circulating CTL probably via cell to cell contact, and may help avoid massive nonspecific inflammatory cell infiltration and activation.…”

Mouse B7-H3 induces antitumor immunity

“…In contrast, the immune system remains completely ignorant of the parental nontransfected tumor cells, which grow unchecked. [13][14][15] Intratumoral gene transfer of mouse B7-1 and -2, which can eradicate already established tumors, has been shown to costimulate antitumor activity mediated by CD8 + T cells and NK cells, accompanied by augmented tumor-specific cytolytic T-cell (CTL) activity involving both the perforin and Fas-ligand pathways. [16][17][18][19][20] B7-H3 is also a potential anticancer agent as it can induce many of the pathways required for a potent antitumor immune response.…”

Immunotherapy against murine leukemia

“…Recent experiments have shown that several poorly immunogenic solid tumors can be recognized by MHC-class restricted CD8 + CTL if the tumors are engineered to secrete one of several cytokines or costimulatory molecules. [20][21][22][23][24][25][26][27][28][29] In addition, secretion of cytokines by the tumor cells stimulated the host's immune system to identify and kill the untransduced parental cells upon reimplantation; and even more, a rejection of established cancer can occur by inducing a systemic anticancer immune response by vaccination with cytokine-transduced tumor cells. 21,[22][23][24][25][26][27][28][29][30] Leukemic cells may escape immune surveillance by not expressing leukemia-specific antigens or by not expressing signals that are essential for activation of the host immune system.…”

“…[20][21][22][23][24][25][26][27][28][29] In addition, secretion of cytokines by the tumor cells stimulated the host's immune system to identify and kill the untransduced parental cells upon reimplantation; and even more, a rejection of established cancer can occur by inducing a systemic anticancer immune response by vaccination with cytokine-transduced tumor cells. 21,[22][23][24][25][26][27][28][29][30] Leukemic cells may escape immune surveillance by not expressing leukemia-specific antigens or by not expressing signals that are essential for activation of the host immune system. 31 At the molecular level, the defective signaling of leukemic cells might be attributable to (1) down-regulation of major histocompatibility complex (MHC) molecules; (2) alteration of antigen-presenting pathways, resulting in an inability to present tumor-specific antigens to host T cells; (3) absence of costimulatory or adhesion molecules that are essential for activation of the host immune system; or (4) production of factors that modify host immune responses.…”