The Genomic Landscape of Antigenic Targets for T Cell-Based Leukemia Immunotherapy

Abstract

Intensive fundamental and clinical research in cancer immunotherapy has led to the emergence and evolution of two parallel universes with surprisingly little interactions: the realm of hematologic malignancies and that of solid tumors. Treatment of hematologic cancers using allogeneic hematopoietic cell transplantation (AHCT) serendipitously led to the discovery that T cells specific for minor histocompatibility antigens (MiHAs) could cure hematopoietic cancers. Besides, studies based on treatment of solid tumor with ex vivo-expanded tumor infiltrating lymphocytes or immune checkpoint therapy demonstrated that anti-tumor responses could be achieved by targeting tumor-specific antigens (TSAs). It is our contention that much insight can be gained by sharing the tremendous amount of data generated in the two-abovementioned universes. Our perspective article has two specific goals. First, to discuss the value of methods currently used for MiHA and TSA discovery and to explain the key role of mass spectrometry analyses in this process. Second, to demonstrate the importance of broadening the scope of TSA discovery efforts beyond classic annotated protein-coding genomic sequences.

Keywords: RNA sequencing; genomics; major histocompatibility complex; mass spectrometry; minor histocompatibility antigen; peptide; proteogenomics; tumor-specific antigen.