{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T16:44:37Z","timestamp":1788799477671,"version":"build-2803163510"},"reference-count":45,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["81922058"],"award-info":[{"award-number":["81922058"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Science Fund for Distinguished Young Scholars","award":["T2125002"],"award-info":[{"award-number":["T2125002"]}]},{"DOI":"10.13039\/501100018537","name":"National Science and Technology Major Project","doi-asserted-by":"crossref","award":["2019YFC1315702"],"award-info":[{"award-number":["2019YFC1315702"]}],"id":[{"id":"10.13039\/501100018537","id-type":"DOI","asserted-by":"crossref"}]},{"name":"National Youth Top-Notch Talent Support Program","award":["283812"],"award-info":[{"award-number":["283812"]}]},{"name":"Peking University Clinical Medicine plus X Youth Project","award":["PKU2019LCXQ012"],"award-info":[{"award-number":["PKU2019LCXQ012"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,22]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>Immune checkpoint blockade is an emerging treatment for T cell non-Hodgkin\u2019s lymphoma (T-NHL), but some patients with T-NHL have experienced hyperprogression with undetermined mechanisms upon anti\u2013PD-1 therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Single-cell RNA-Seq, whole-genome sequencing, whole-exome sequencing, and functional assays were performed on primary malignant T cells from a patient with advanced cutaneous T cell lymphoma who experienced hyperprogression upon anti\u2013PD-1 treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The patient was enrolled in a clinical trial of anti\u2013PD-1 therapy and experienced disease hyperprogression. Single-cell RNA-Seq revealed that PD-1 blockade elicited a remarkable activation and proliferation of the CD4\n                      <jats:sup>+<\/jats:sup>\n                      malignant T cells, which showed functional PD-1 expression and an exhausted status. Further analyses identified somatic amplification of\n                      <jats:italic>PRKCQ<\/jats:italic>\n                      in the malignant T cells.\n                      <jats:italic>PRKCQ<\/jats:italic>\n                      encodes PKC\u03b8; PKC\u03b8 is a key player in the T cell activation\/NF-\u03baB pathway.\n                      <jats:italic>PRKCQ<\/jats:italic>\n                      amplification led to high expressions of PKC\u03b8 and p-PKC\u03b8 (T538) on the malignant T cells, resulting in an oncogenic activation of the T cell receptor (TCR) signaling pathway. PD-1 blockade in this patient released this signaling, derepressed the proliferation of malignant T cells, and resulted in disease hyperprogression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Our study provides real-world clinical evidence that PD-1 acts as a tumor suppressor for malignant T cells with oncogenic TCR activation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov (NCT03809767).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>The National Natural Science Foundation of China (81922058), the National Science Fund for Distinguished Young Scholars (T2125002), the National Science and Technology Major Project (2019YFC1315702), the National Youth Top-Notch Talent Support Program (283812), and the Peking University Clinical Medicine plus X Youth Project (PKU2019LCXQ012) supported this work.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.164793","type":"journal-article","created":{"date-parts":[[2023,1,17]],"date-time":"2023-01-17T12:01:10Z","timestamp":1673956870000},"source":"Crossref","is-referenced-by-count":32,"title":["Hyperprogression of cutaneous T cell lymphoma after anti\u2013PD-1 treatment"],"prefix":"10.1172","volume":"8","author":[{"given":"Yumei","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Dermatology and Venereology, Peking University First Hospital, Beijing, China."},{"name":"Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, China."},{"name":"National Clinical Research Center for Skin and Immune Diseases, Beijing, 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