Role of Bone Marrow-Derived Cells in Presenting MHC Class I-Restricted Tumor Antigens

Abstract

Many tumors express tumor-specific antigens capable of being presented to CD8+ T cells by major histocompatibility complex (MHC) class I molecules. Antigen presentation models predict that the tumor cell itself should present these antigens to T cells. However, when conditions for the priming of tumor-specific responses were examined in mice, no detectable presentation of MHC class I-restricted tumor antigens by the tumor itself was found. Rather, tumor antigens were exclusively presented by host bone marrow-derived cells. Thus, MHC class I-restricted antigens are efficiently transferred in vivo to bone marrow-derived antigen-presenting cells, which suggests that human leukocyte antigen matching may be less critical in the application of tumor vaccines than previously thought.

Anti-tumour activity against B16-F10 melanoma with a GM-CSF secreting allogeneic tumour cell vaccine

“…The success of allogeneic K1735-M2 vaccine cells is likely to be due to 'cross-priming' tumour antigen presentation whereby antigens on the tumour vaccine cells are released in the vicinity of the vaccination site and then processed and presented to naive T cells by autologous professional APC [5][6][7]25 making any requirement for MHC matching between the vaccine tumour cells and the vaccine recipient unnecessary. Although we do not know the possible cross-reactive antigen(s) being targeted by the immune response, the in vitro T cell work showed that the allogeneic vaccine generated B16-F10 specific CTLs.…”

“…The involvement of both CD4+ve and CD8+ve T cells in mediating the effects of the allogeneic vaccine led us to believe that it operated via the indirect pathway of antigen presentation also known as 'cross-priming' 5,6 which involves the autologous APC. GM-CSF cytokine improves the recruitment and maturation of professional APCs 24 as well as the efficacy of autologous whole cell melanoma vaccines.…”

“…4 The use of allogeneic vaccines would not only overcome these problems, it also has immunological rationale in the body of data illustrating that tumour antigens from tumour vaccine cells are presented to naive T cells by the host's own antigen presenting cells. [5][6][7][8] This phenomenon of 'cross-priming' eliminates the need for MHC matching in the case of allogeneic vaccine strategy. However, this approach demands that the allogeneic tumour cells used as vaccine share some cross-reactive antigens with the autologous tumour.…”

Intravesical liposome-mediated interleukin-2 gene therapy in orthotopic murine bladder cancer model

“…CD8 + CTL play an important role in tumor antigen recognition in the context of MHC class I molecules expressed on the surface of the target tumor cells. 24 To date, many studies involving the treatment of tumor-bearing animals with nonimmunogenic tumor cells engineered to secrete various cytokines have demonstrated the inhibition of pre-established tumors. [1][2][3][4][5][6]10,25 In our previous experiments, ex vivo genetically modified IL-2 or GM-CSF secreting MBT-2 cell preparations were shown to induce effective immune responses against original MBT-2 tumors and cure up to 50% of animals with pre-established MBT-2 bladder tumors.…”

Herpes simplex virus type-1 amplicon vectors for vaccine generation in acute lymphoblastic leukemia

“…43 This is in accordance with the observation that following intratumoral injection of so called oncolytic herpesvirus vectors for local tumor control, systemic antitumor activity with rejection of metastases at distant sites has been observed. 44 In this setting HSV vector-induced lysis of solid tumor cells is thought to initiate crosspriming events, [45][46][47] resulting in uptake of tumor-cell-derived proteins by professional antigen-presenting cells. 48 The observed expansion of activated T, NK and antigen-presenting cells in mice splenocytes supports a similar scenario underlying the antineoplastic effects induced by the replication-defective HSV-1 helper virus-dependent vectors.…”