Role of Tumor Cell Apoptosis in Tumor Antigen Migration to the Draining Lymph Nodes

Abstract

Establishment of an immune response against cancer may depend on the capacity of dendritic cells to transfer tumor Ags into T cell-rich areas. To check this possibility, we used a colon cancer cell variant that yields tumors undergoing complete T cell-dependent rejection when injected into syngeneic rats. We previously demonstrated that immunogenicity of these tumors depended on the early apoptosis of a part of these tumor cells. In this paper we show that fluorescent tumor cell proteins are released from FITC-labeled tumor cells and undergo engulfment by tumor-infiltrating monocytes without a phenotype of mature dendritic cells or macrophages. Fluorescence-labeled mononuclear cells with a phenotype of MHC class II+ dendritic cells are also found in the T cell areas of the draining lymph nodes. Interestingly, no fluorescent cell can be found in lymph nodes after a s.c. injection of Bcl2-transfected apoptosis-resistant tumor cells that yielded progressive tumors. Proliferation of tumor-immune T lymphocytes was induced by dendritic cells isolated from the draining lymph nodes recovered after a s.c. injection of apoptosis-sensitive, but not apoptosis-resistant, tumor cells. These results show that tumor cell apoptosis releases proteins that are engulfed by inflammatory cells in the tumor, then transported to lymph node T cell areas where they can induce a specific immune response leading to tumor rejection.

Biomarker selection for detection of occult tumour cells in lymph nodes of colorectal cancer patients using real-time quantitative RT–PCR

“…Moreover, since analyses are performed at the mRNA level instead of at the protein level positive results are likely to reflect the presence of living tumour cells. It has been shown that dendritic cells/macrophages can transport protein components from apoptotic epithelial cells to lymph nodes (Bonnotte et al, 2000;Huang et al, 2000). A yet unresolved question in using qRT -PCR for the purpose of detecting disseminated tumour cells in regional lymph nodes is, however, which biomarker mRNA to use.…”

Identification of Tumor-Infiltrating Macrophages as the Killers of Tumor Cells After Immunization in a Rat Model System

“…The spontaneous regression of the REG tumors is related to a T cell-dependent immune response because REG cells give rise to progressive tumors in the nude mice or cyclosporine-treated syngeneic rats (7). Induction of an efficient anti-tumor immune response by REG cells is now well documented (8,9). We have demonstrated that tumor Ags liberated by early death of a part of these tumor cells following s.c. injection are endocytosed by phagocytic cells which differentiate into dendritic cells.…”

Modulation of apoptosis by procaspase-2 short isoform: selective inhibition of chromatin condensation, apoptotic body formation and phosphatidylserine externalization

“…Processing of phagocytosed apoptotic bodies has been shown also to yield antigens that access the cytosol and the MHC class I pathway of engul®ng cells (Albert et al, 1998), can be recognized by antigen-speci®c lymphocytes (Ronchetti et al, 1999) and can induce dendritic cell maturation (Rovere et al, 1998). The importance of apoptotic bodies for tumor cell immunogenicity (Bonnotte et al, 1998(Bonnotte et al, , 2000 suggests that the procaspase-2S / procaspase-2L ratio, that is modulated by mammalian splicing factors (Jiang et al, 1998), could determine the quality of a speci®c antitumor immune response.…”