LC-MSMS of the MHC-I immunopeptidome of human iPSCs

The development of cancer immunotherapeutics is limited by the discovery of actionable tumor-specific antigens (TSAs), which need to be presented at high levels on cancer cells, but not presented by normal tissues or presented at levels below the threshold for T-cell recognition to prevent autoimmunity. Accumulating evidence indicates that pluripotent stem cells (PSCs), namely embryonic stem cells (ESCs) and induced PSCs (iPSCs), express a class of pluripotency-associated MHC-I-associated peptides (paMAPs) that can be recognized by tumor-specific T cells. Hence, being strictly confined to the embryonic stage of development and absent from healthy adult tissues, paMAPs shared by iPSCs and tumors would represent ideal targets for the development of TSA-based vaccines against a wide range of cancers. We performed immunopeptidomic analyses of human iPSCs and we identified a set of paMAPs that could serve for the design of TSA-based vaccines against many cancers.