Olga Tanaskovic

Over the last decade, the cell-cycle inhibitor p21 has been shown to sustain leukaemia propagation with two distinct mechanisms. On one hand, p21 was shown to be critical for maintaining increased self-renewal capacities of leukaemia stem cells. Indeed, the absence of p21 in leukaemia stem cells leads to their functional exhaustion, which results in loss of leukaemia transplantability in syngeneic mice. On the other hand, p21 expression is crucial for evading the surveillance mechanisms of the immune system, thus ensuring tumor growth. Specifically, lack of p21 in the leukemic microenvironment activates a potent CD4+ T-cell mediated immunological response against tumor in syngeneic context (unpublished data from the host laboratory). To translate the observed p21- dependent anti-tumoral immunity into novel immune-therapies against cancer, underlying mechanisms needed to be unrevealed.

In my thesis work, I dissected the cellular bases of the p21-dependent anti-tumor immunity. I disclosed a crucial role of the p21-/- tumor microenvironment in triggering activation of an anti-tumor immunological response. In particular, for the first time I identified rare iron-loaded CD68+ tumor- associated macrophages (iTAMs) in the p21-null context as key mediators of a potent immunological mechanisms of cancer clearance. By unravelling crucial players of the p21-dependent anti-tumor immunity, my work set the basis for the future design of novel anti-cancer vaccines. Such vaccines will grant more efficient and less toxic treatment for cancer patients.