{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T14:27:40Z","timestamp":1777904860278,"version":"3.51.4"},"reference-count":50,"publisher":"BMJ","issue":"1","license":[{"start":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T00:00:00Z","timestamp":1672617600000},"content-version":"unspecified","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Beijing Natural Science Foundation","award":["7202024"],"award-info":[{"award-number":["7202024"]}]},{"name":"Beijing Natural Science Foundation","award":["7214217"],"award-info":[{"award-number":["7214217"]}]},{"DOI":"10.13039\/501100009601","name":"Beijing Municipal Administration of Hospitals\u2019 Ascent Plan","doi-asserted-by":"crossref","award":["DFL20220901"],"award-info":[{"award-number":["DFL20220901"]}],"id":[{"id":"10.13039\/501100009601","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Beijing Medical Award Foundation","award":["YXJL-2020-0889-0106"],"award-info":[{"award-number":["YXJL-2020-0889-0106"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972562"],"award-info":[{"award-number":["81972562"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81972566"],"award-info":[{"award-number":["81972566"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82073011"],"award-info":[{"award-number":["82073011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82272676"],"award-info":[{"award-number":["82272676"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2022,12,7]]},"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Accumulating data suggest that mucosal melanoma, well known for its poor response to immune checkpoint blockade (ICB) and abysmal prognosis, is a heterogeneous subtype of melanoma with distinct genomic and clinical characteristics between different anatomic locations of the primary lesions. Primary malignant melanoma of the esophagus (PMME) is a rare, highly aggressive disease with a poorer prognosis compared with that of non-esophageal mucosal melanoma (NEMM). In this study, we retrospectively analyzed the efficacy of anti-programmed death (PD)-1 in patients with PMME and explored its molecular basis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The response and survival of patients with PMME and NEMM under anti-PD-1 monotherapy were retrospectively analyzed. To explore the molecular mechanisms of the difference in therapeutic efficacy between PMME and NEMM, we performed genomic analysis, bulk RNA sequencing, and multiplex immunohistochemistry staining.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We found that PMME (n=28) responded better to anti-PD-1 treatment than NEMM (n=64), with a significantly higher objective response rate (33.3% (95% CI 14.3% to 52.3%) vs 6.6% (95% CI 0.2% to 12.9%)) and disease control rate (74.1% (95% CI 56.4% to 91.7%) vs 37.7% (95% CI 25.2% to 50.2%)). Genomic sequencing analysis revealed that the genomic aberration landscape of PMME predominated in classical cancer driver genes, with approximately half of PMME cases harboring mutations in <jats:italic>BRAF<\/jats:italic>, <jats:italic>N\/KRAS<\/jats:italic>, and <jats:italic>NF1<\/jats:italic>. In contrast, most NEMM cases were triple wild-type. Transcriptome analysis revealed that, compared with NEMM, PMME displayed more significant proliferation and inflammatory features with higher expression of genes related to antigen presentation and differentiation, and a less immunosuppressive signature with lower expression of inhibitory immune checkpoints and dedifferentiation-related genes. The multiplex immunohistochemical analysis also demonstrated higher CD8<jats:sup>+<\/jats:sup> T-cell infiltration in PMME than in NEMM.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>PMME is an outlier of mucosal melanoma showing a malicious phenotype but a particularly high response rate to ICB because of its distinct molecular characteristics. Patient stratification based on anatomic origin can facilitate clinical decision-making in patients with mucosal melanoma following the verification of our results in future prospective studies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2022-005937","type":"journal-article","created":{"date-parts":[[2023,1,2]],"date-time":"2023-01-02T10:50:54Z","timestamp":1672656654000},"page":"e005937","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":9,"title":["Molecular underpinnings of exceptional response in primary malignant melanoma of the esophagus to anti-PD-1 monotherapy"],"prefix":"10.1136","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7586-7889","authenticated-orcid":false,"given":"Jie","family":"Dai","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer 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