PD-1, cancer, and self-nonself discrimination by T cells

Abstract

Recently, we have learned that the antibody-mediated PD-1 blockade in cancer patients elicits immune reactions against mutated proteins derived from the mutated genome of cancer cells. This implies that PD-1 inhibits immune reactions against the mutant antigens originated from the mutated genome in cancer patients. Then, why does PD-1 have to cancel such cancer cell-specific immune reactions? Is PD-1 on our side, or on the side of cancer cells? We know that PD-1 is a negative regulator of immune reactions, but what kind of immune reactions are negatively regulated by PD-1? In order to answer these questions, I first review the history of the PD-1 research briefly. Then, I present a new hypothesis about the physiological function(s) of PD-1 and try to test its validity by performing a couple of novel experiments.