{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n CTAG1A, which encodes the cancer/testis antigen NY‐ESO‐1, is normally restricted to germ cells yet is aberrantly expressed in a variety of human tumors—including melanoma, ovarian cancer, multiple myeloma, hepatocellular carcinoma, synovial sarcomas, and certain subtypes of breast cancer."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": " This anomalous expression renders NY‐ESO‐1 highly immunogenic and an attractive target for antigen‐specific immunotherapy, as evidenced by its ability to elicit spontaneous as well as vaccine‐induced CD8⁺ and CD4⁺ T‐cell responses along with humoral immunity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, the presence of NY‐ESO‐1–specific T cells correlates with favorable clinical outcomes and improves responses to immune checkpoint blockade, supporting combined therapeutic strategies that counter T‐cell exhaustion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Epigenetic mechanisms play a critical role in regulating CTAG1A expression; for example, a switch in promoter occupancy between the insulator protein CTCF and its paralogue BORIS facilitates its tumor‐restricted activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " Tumor cells display only limited numbers of NY‐ESO‐1‐derived peptide–MHC complexes on their membranes—often as few as 10–50 molecules per cell—yet these low levels are sufficient for recognition by high‐affinity T cells."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the dual role of CTAG1A/NY‐ESO‐1 as both an immunogenic tumor marker and a functional driver of cytotoxic T‐cell responses. Its frequent expression in advanced disease and its ability to serve as a target for vaccines and adoptive T‐cell therapies highlight its importance in current and emerging immunotherapeutic approaches (1,2,3,4,5,6,7,8,9).\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julien Fourcade, Zhaojun Sun, Mourad Benallaoua, et al. 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