Potential of Z-100, extracted from Mycobacterium tuberculosis strain Aoyama B, as a hot tumor inducer

The tumor microenvironment is one of the most important factors determining the efficacy of cancer immunotherapy. In particular, variability in efficacy has been linked to whether tumors are hot or cold, with hot tumors exhibiting greater T cell infiltration and responding better to immunotherapy. Z-100 extracted from Mycobacterium tuberculosis Aoyama B strain has been reported to increase cytokine production from immune cells. In this study, we examined its effect on the tumor microenvironment and its potential as a hot tumor inducer. The antitumor effect of Z-100 was confirmed in a mouse oral squamous cell carcinoma (Sq-1979) tumor model by starting administration before tumor injection. Treated tumors were collected to identify infiltrating CD8⁺ T cells. The antitumor effects of Z-100 were additionally examined in mice treated with anti-CD8 antibody and in IL-12p40 knockout (KO) mice. We found that Z-100 had strong antitumor effects and increased the proportion of CD8⁺ T cells in tumors. Moreover, the CD8⁺ T cells infiltrating tumors were identified as effector memory CD8⁺ T cells. Furthermore, the antitumor effects of Z-100 were abolished in mice treated with an anti-CD8 antibody and in IL-12p40 KO mice. Thus, Z-100 induces its antitumor effects by increasing tumor-infiltrating CD8⁺ T cells, suggesting that Z-100 may be a useful cancer therapy by acting as a hot tumor inducer.