Deregulation of signaling pathways is a hallmark of malignant transformation. Signaling-associated
phosphoproteins can be degraded to generate
cancer-specific
phosphopeptides that are presented by major histocompatibility complex (MHC) class I and II molecules and recognized by T cells; however, the contribution of these
phosphoprotein-specific T cells to immune surveillance is unclear. We identified 95
phosphopeptides presented on the surface of primary hematological
tumors and normal tissues, including 61 that were
tumor-specific.
Phosphopeptides were more prevalent on more aggressive and malignant samples. CD8(+) T cell lines specific for these
phosphopeptides recognized and killed both
leukemia cell lines and
human leukocyte antigen-matched primary
leukemia cells ex vivo. Notably, healthy individuals showed robust CD8(+) T cell responses against many of these
phosphopeptides within the circulating memory compartment. This immunity was significantly reduced or absent in some
leukemia patients. This reduction correlated with clinical outcome; however, immunity was restored after allogeneic
stem cell transplantation. These results suggest that
phosphopeptides may be targets of
cancer immune surveillance in humans, and point to their importance for development of
vaccine-based and T cell adoptive transfer
immunotherapies.