{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:20:27Z","timestamp":1789842027409,"version":"4.0.1"},"reference-count":48,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T00:00:00Z","timestamp":1766620800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    PD\u20101 inhibitors have reshaped the treatment landscape of classical Hodgkin lymphoma, yet a substantial proportion of patients exhibit primary or acquired resistance driven by tumor\u2010intrinsic alterations, immunosuppressive microenvironmental signals, metabolic constraints, and EBV\u2010mediated modulation. This review summarizes key mechanisms underlying PD\u20101 resistance and highlights emerging biomarkers\u2014including early\n                    <jats:sup>18<\/jats:sup>\n                    F\u2010FDG PET response, circulating tumor DNA kinetics, molecular subtyping, and spatial immune profiling\u2014that enable early identification of nonresponders and support precision immunotherapy. Novel therapeutic strategies such as macrophage\u2010targeted agents, metabolic modulators, bispecific antibodies, low\u2010dose PD\u20101 regimens, and CD30\u2010directed CAR\u2010T cells show promise in overcoming resistance, particularly when integrated into adaptive, biomarker\u2010guided treatment algorithms. Early incorporation of PET and ctDNA monitoring may inform timely treatment adaptation, while combination approaches addressing macrophage\u2010driven suppression or redundant immune checkpoints should be considered in biologically high\u2010risk patients. Overall, a deeper mechanistic understanding coupled with biomarker\u2010driven stratification is essential to optimize PD\u20101\u2010based therapy and improve long\u2010term outcomes in cHL.\n                  <\/jats:p>","DOI":"10.1111\/ejh.70101","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T05:27:10Z","timestamp":1766726830000},"page":"357-367","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Beyond PD\u20101: Mechanisms of Resistance to Checkpoint Blockade in Classical Hodgkin Lymphoma and Next\u2010Generation Immune Strategies"],"prefix":"10.1111","volume":"116","author":[{"given":"Santino","family":"Caserta","sequence":"first","affiliation":[{"name":"Hematology Unit, Department of Onco\u2010Hematology AO of Cosenza  Cosenza Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica 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