Phosphopeptide Neoantigens As Emerging Targets in Cancer Immunotherapy

Protein post-translational modifications play a vital role in various cellular events essential for maintaining cellular physiology and homeostasis. In cancer cells, aberrant post-translational modifications such as glycosylation, acetylation, and phosphorylation on proteins can result in the generation of antigenic peptide variants presented in complex with MHC molecules. These modified peptides add to the class of tumorspecific antigens and offer promising avenues for targeted anti- cancer therapies. In this review, we focus on the role of phosphorylated peptides (p-peptides) in cancer immunity. We discuss the mechanisms by which the phosphorylated moiety modifies the structural features and binding properties of p-peptides with MHC, compared to their non-phosphorylated counterparts. Additionally, we review recent work on how the HLA-B*07-specific p-peptide, pMLL, interacts with its cognate TCR. Altogether, p-peptides are emerging as a novel class of tumor-specific antigens, expanding the range of targets in cancer immunotherapy.