Autoimmune T-cells induced by low dose immune checkpoint blockade could be a powerful therapeutic tool in cancer through activation of eliminative inflammation and immunity

Tibor Bakacs, Katalin Kristóf, Jitendra N Mehrishi, Tamas Szabados, Csaba Kerepesi, Enikoe Regoes, Gabor Tusnady


The immune system has been hypothesized to have evolved to purge nascent selfish host cells, while immune defense against xenogeneic alien pathogens appeared later in evolution. To prevent a natural tendency of tumor development, we proposed that immune surveillance is carried out by a coupled system of complementary T cells and host cells. An ongoing internal dialogue between T cells and host cells keeps T cells alive via stimulation by self-antigens while putting strict limits on variations of host cells by eliminating selfish cells. Convincing evidence for such dialogue, which temporarily activates T cells, emerged from the widespread autoimmune events in 72% of advanced melanoma patients treated with the immune checkpoint blocking ipilimumab. This blockade turned physiologic T cell activation into uncontrolled autoimmunity. We suggest that harnessing the unleashed autoimmune power of T cells would be more rewarding to eliminate cancer than copying infectious vaccination to induce tumor specific immunity.


cancer deaths; infectious disease deaths; one-signal T cell model; ipilimumab; harnessing autoimmune T cells; fallacy of tumor immunology

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