{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:59:09Z","timestamp":1790521149413,"version":"4.1.0"},"reference-count":46,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"34","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO"],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:sec><jats:title>PURPOSE<\/jats:title><jats:p> Understanding the immunobiology of the 15% to 30% of patients with follicular lymphoma (FL) who experience progression of disease within 24 months (POD24) remains a priority. Solid tumors with low levels of intratumoral immune infiltration have inferior outcomes. It is unknown whether a similar relationship exists between POD24 in FL. <\/jats:p><\/jats:sec><jats:sec><jats:title>PATIENTS AND METHODS<\/jats:title><jats:p> Digital gene expression using a custom code set\u2014five immune effector, six immune checkpoint, one macrophage molecules\u2014was applied to a discovery cohort of patients with early- and advanced-stage FL (n = 132). T-cell receptor repertoire analysis, flow cytometry, multispectral immunofluorescence, and next-generation sequencing were performed. The immune infiltration profile was validated in two independent cohorts of patients with advanced-stage FL requiring systemic treatment (n = 138, rituximab plus cyclophosphamide, vincristine, prednisone; n = 45, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), with the latter selected to permit comparison of patients experiencing a POD24 event with those having no progression at 5 years or more. <\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p> Immune molecules showed distinct clustering, characterized by either high or low expression regardless of categorization as an immune effector, immune checkpoint, or macrophage molecule. Low programmed death-ligand 2 (PD-L2) was the most sensitive\/specific marker to segregate patients with adverse outcomes; therefore, PD-L2 expression was chosen to distinguish immune infiltration<jats:sup>HI<\/jats:sup> (ie, high PD-L2) FL biopsies from immune infiltration<jats:sup>LO<\/jats:sup> (ie, low PD-L2) tumors. Immune infiltration<jats:sup>HI<\/jats:sup> tissues were highly infiltrated with macrophages and expanded populations of T-cell clones. Of note, the immune infiltration<jats:sup>LO<\/jats:sup> subset of patients with FL was enriched for POD24 events (odds ratio [OR], 4.32; c-statistic, 0.81; P = .001), validated in the independent cohorts (rituximab plus cyclophosphamide, vincristine, prednisone: OR, 2.95; c-statistic, 0.75; P = .011; and rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone: OR, 7.09; c-statistic, 0.88; P = .011). Mutations were equally proportioned across tissues, which indicated that degree of immune infiltration is capturing aspects of FL biology distinct from its mutational profile. <\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p> Assessment of immune-infiltration by PD-L2 expression is a promising tool with which to help identify patients who are at risk for POD24. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.18.02365","type":"journal-article","created":{"date-parts":[[2019,8,28]],"date-time":"2019-08-28T19:55:26Z","timestamp":1567022126000},"page":"3300-3309","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":116,"title":["Progression of Disease Within 24 Months in Follicular Lymphoma Is Associated With Reduced Intratumoral Immune Infiltration"],"prefix":"10.1200","volume":"37","author":[{"given":"Joshua W.D.","family":"Tobin","sequence":"first","affiliation":[{"name":"Mater Research, University of Queensland, Brisbane, QLD, Australia"},{"name":"Princess Alexandra Hospital, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colm","family":"Keane","sequence":"additional","affiliation":[{"name":"Mater Research, University of Queensland, Brisbane, QLD, Australia"},{"name":"Princess Alexandra Hospital, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay","family":"Gunawardana","sequence":"additional","affiliation":[{"name":"Mater Research, University of Queensland, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mollee","sequence":"additional","affiliation":[{"name":"Princess Alexandra Hospital, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simone","family":"Birch","sequence":"additional","affiliation":[{"name":"Princess Alexandra Hospital, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thanh","family":"Hoang","sequence":"additional","affiliation":[{"name":"Diamantina Institute, University of Queensland, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justina","family":"Lee","sequence":"additional","affiliation":[{"name":"Diamantina Institute, University of Queensland, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Ochsner Health System, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Huang","sequence":"additional","affiliation":[{"name":"Ochsner Health System, New Orleans, LA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentine","family":"Murigneux","sequence":"additional","affiliation":[{"name":"Diamantina Institute, University of Queensland, Brisbane, QLD, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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