In vivo induction of antitumor immunity and protection against tumor growth by injection of CD154-expressing tumor cells.
As they should enhance tumor-specific antigen presentation by dendritic cells, tumor cell lines genetically modified to express CD154 molecules have been used in an attempt to induce protective antitumor immunity. Two murine models were used: the major histocompatibility complex (MHC) class I negative melanoma B16F10 and the MHC class I positive mammary adenocarcinoma TS/A. CD154 or mock-transfected B16F10 or TS/A cells were injected subcutaneously into H-2-compatible B6D2 mice. CD154 expression by tumor cells induced a complete rejection (in the TS/A model) or a striking reduction (in the B16F10 model) of modified tumors growth, but also a significant protection against the growth of mock tumor cells injected simultaneously, either mixed with the CD154-expressing tumor cells, or in the other flank of mice. Thirty days after CD154-expressing tumor rejection, splenic lymphocytes from surviving tumor-free mice were able to inhibit tumor proliferation in vitro and significant amounts of IFN-gamma were detected in the sera of these mice. Growth kinetics of mock and CD154-expressing tumors in immunocompetent versus nude mice suggest that T lymphocytes and natural killer cells responses are implicated in this antitumor immunity. The injection of CD154-expressing tumor cell induced an antitumor protective response, both locally and distant from the injection site. The effect was most pronounced in MHC class I expressing TS/A tumor model.
Grangeon
Cendrine
C
Laboratoire d'Oncologie Cellulaire et Moléculaire, EA/UPRES 2048, Institut Claudius Regaud 20-24, rue du Pont Saint-Pierre, Toulouse Cedex 31052, France.
Cormary
Carine
C
Douin-Echinard
Vickorine
V
Favre
Gilles
G
Couderc
Bettina
B
Tilkin-Mariamé
Anne-Françoise
AF
D000818:Animals; D023201:CD40 Ligand / Q000378:metabolism*; D017931:DNA Primers; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D005805:Genes, MHC Class I / Q000235:genetics*; D005822:Genetic Vectors; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D008546:Melanoma, Experimental / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013154:Spleen / Q000276:immunology* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D017931:DNA Primers; D023201:CD40 Ligand