{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:48:51Z","timestamp":1790412531476,"version":"4.1.0"},"reference-count":55,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO Oncol Adv"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>PD-L1 and PD-L2 are inhibitory ligands that interact with PD-1 receptors, enabling immune escape. Although PD-L1 has been extensively studied, much less is known about PD-L2. PD-L2 expression could lead to incomplete blockade of the PD-1 axis by anti\u2013PD-L1 agents and also influence the activity of anti\u2013PD-1 agents.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed PD-L2 transcriptomic expression in a pan-cancer cohort (N = 514; 489 patients with advanced\/metastatic disease and clinical correlates available) for associations with immunomodulatory variables and outcome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The most common tumors were colorectal (27% [140 of 514]), pancreatic (11% [55 of 514]), and breast cancer (9.5% [49 of 514]). High PD-L2 expression (\u226575th RNA percentile rank) occurred in 19.5% (100 of 514) of patients; PD-L2 expression varied across and within tumor types. High PD-L2 independently\/significantly correlated with high PD-L1, PD-1, CD4, and T-cell immunoglobulin and mucin-containing protein 3 (TIM-3) RNA levels (both as dichotomized and linear variables), high tumor mutational burden (TMB; \u226510 mutations\/Mb), and a breast cancer diagnosis. In 217 patients who received immune checkpoint blockade (mainly anti\u2013PD-1-based regimens), high versus moderate\/low PD-L2 predicted longer overall survival (OS) (but not progression-free survival) in univariate analysis (median, 1.88 years [95% CI, 1.37 to not estimable] versus 1.21 years [95% CI, 0.95 to 1.54];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .02). In 272 patients who never received immunotherapy, high PD-L2 expression was not prognostic for OS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>High PD-L2 transcripts were more common in breast cancer and associated with high expression of other immune-relevant factors: PD-L1, PD-1, CD4, and TIM-3, and with TMB \u226510 mutations\/Mb. High PD-L2 levels correlated with longer OS in immunotherapy-treated patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/oa-25-00151","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:58:06Z","timestamp":1768510686000},"source":"Crossref","is-referenced-by-count":4,"title":["PD-L2 Landscape and Correlation With Outcome: An Immunomic Analysis"],"prefix":"10.1200","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0902-6912","authenticated-orcid":true,"given":"Anannya","family":"Patwari","sequence":"first","affiliation":[{"name":"MCW Cancer Center and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6746-3224","authenticated-orcid":true,"given":"Daisuke","family":"Nishizaki","sequence":"additional","affiliation":[{"name":"Center for Personalized Cancer Therapy, Division of Hematology and Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taylor","family":"Jensen","sequence":"additional","affiliation":[{"name":"Labcorp, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9072-0631","authenticated-orcid":true,"given":"Paul","family":"DePietro","sequence":"additional","affiliation":[{"name":"Labcorp, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarabjot","family":"Pabla","sequence":"additional","affiliation":[{"name":"Labcorp, Buffalo, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1193-1815","authenticated-orcid":true,"given":"Shumei","family":"Kato","sequence":"additional","affiliation":[{"name":"Center for Personalized Cancer Therapy, Division of Hematology and Oncology, Department of Medicine, University of California San Diego, Moores Cancer Center, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-1214","authenticated-orcid":true,"given":"Razelle","family":"Kurzrock","sequence":"additional","affiliation":[{"name":"MCW Cancer Center and Genomic Sciences and Precision Medicine Center, Medical College of Wisconsin, Milwaukee, WI"},{"name":"WIN Consortium, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_7_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24061190"},{"key":"e_1_3_7_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3239"},{"key":"e_1_3_7_4_2","first-page":"727","article-title":"PD-1\/PD-L1 pathway: Current researches in cancer","volume":"10","author":"Han Y","year":"2020","unstructured":"Han Y, Liu D, Li L: PD-1\/PD-L1 pathway: Current researches in cancer. 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