Tumor-infiltrating dendritic cells are defective in their antigen-presenting function and inducible B7 expression in rats.
Tumors are tolerated by the immune system notwithstanding the expression of tumor-associated antigens. PROb tumor cells, derived from a rat colon carcinoma, are rejected by tumor-immune hosts but give rise to progressive tumors in naive hosts. Paradoxically, these tumors are heavily infiltrated by dendritic cells that express MHC class II and ICAM-1. These tumor-infiltrating dendritic cells (TiDCs) could be expected to process and present to T cells the antigens released by the adjacent tumor cells. Indeed, we report here that TiDCs, compared with splenic dendritic cells, are poor stimulators of primary allogeneic T-cell proliferation and cytokine [interleukin-2 (IL-2) and interferon-gamma] production. Most of them (89-97%) do not express B7, an essential co-stimulatory signal for T cells, even after a culture period allowing B7 up-regulation on epidermal Langerhans cells. GM-CSF in association with tumor necrosis factor-alpha or IL-4, or cell-associated CD40-ligand, all known to be potent stimulators of B7 expression on other dendritic cells, did not restore B7 expression by TiDCs. After a first exposure to TiDCs, allogeneic T-cell response to a second challenge to splenic dendritic cells was decreased. The failure of most dendritic cells infiltrating PROb tumors to express B7, even after stimulation, may contribute to their poor capacity to stimulate T cells and could play a role in the immune tolerance allowing tumor growth.
Chaux
P
P
Department of Biology and Therapy of Cancer, Faculty of Medicine, Dijon, France.
Favre
N
N
Martin
M
M
Martin
F
F
D000230:Adenocarcinoma / Q000276:immunology* / Q000473:pathology; D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D015703:Antigens, CD / Q000096:biosynthesis*; D018122:B7-1 Antigen / Q000096:biosynthesis*; D051940:B7-2 Antigen; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051381:Rats; D011916:Rats, Inbred F344; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; C497966:Cd86 protein, rat; D000949:Histocompatibility Antigens Class II; D008562:Membrane Glycoproteins