title: Synthesis of cytokines during tumour development in mice immunized with the mycobacterial antigen complex A60.
abstract: The authors have previously reported on the ability of A60, an immunodominant antigenic complex of Mycobacterium bovis BCG, to prevent cancer development in mice challenged with EMT 6 tumour cells. Such effect proved to rely on neoplastic cell lysis by cytolytic T lymphocytes and activated macrophages. The involvement of cytokines in triggering the immune response leading to tumour rejection is analysed in the present work. The synthesis of IL-2, IFN-gamma and TNF-alpha was strongly increased in A60-primed mice. Cancer development depressed the blood levels of these three cytokines. In vitro cultures of lymphocytes from lymph nodes and blood of A60-primed mice produced higher levels of these cytokines in the presence of A60, as compared to cultures lacking A60. Such effect was inhibited by co-incubation of lymphocytes with EMT 6 tumour cells In vitro cultures of macrophages yielded higher levels of TNF-alpha in the presence of A60 and co-incubation of these cells with EMT 6 tumour cells also inhibited TNF-alpha production. The enhanced synthesis of IL-2 and IFN-gamma, which promote activation of cytolytic T lymphocytes and macrophages, accounts for the increased tumour cell lysis induced in vivo by A60. The A60-promoted synthesis of TNF-alpha is partly responsible for the latter effect. The inhibitory action of EMT-6 tumour cells on cytokine synthesis is a powerful mechanism of tumour escape from the immune system's control.
authors.affiliation: Medical School University of Louvain, Brussels, Belgium.
authors.forename: H
authors.initials: H
authors.lastname: Maes
authors.forename: C
authors.initials: C
authors.lastname: Cocito
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology* / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis; D008214:Lymphocytes / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D014407:Tumor Cells, Cultured
chemical_list: D000942:Antigens, Bacterial; D016207:Cytokines; D007376:Interleukin-2; C055539:mycobacterial A60 antigen