Synthesis of cytokines during tumour development in mice immunized with the mycobacterial antigen complex A60

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-a 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.