{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T06:02:25Z","timestamp":1780293745567,"version":"3.54.0"},"reference-count":42,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Immune checkpoint inhibitors (ICIs) targeting the PD-1\/PD-L1 axis have shown considerable promise as a therapeutic modality in oncology. Despite their ability to target stem-like CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and give rise to exhaustion-fated effector CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells, a significant subset of patients do not respond or eventually develop resistance, highlighting the need for more efficacious therapies. Eciskafusp alfa (PD1-IL2v) is a novel immunocytokine, engineered for avidity-driven,\n                      <jats:italic>cis<\/jats:italic>\n                      -delivery of IL-2R agonism to PD-1\n                      <jats:sup>+<\/jats:sup>\n                      cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study provides a comprehensive\n                      <jats:italic>ex-vivo<\/jats:italic>\n                      characterization of PD1-IL2v\u2019s target landscape using matched peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) from patients across seven solid tumor indications.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We confirmed that the TIL compartment is significantly enriched with both stem-like CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells and immunosuppressive regulatory T cells (Tregs). Notably, PD-1 receptor density was increased up to three-fold on CD8\n                      <jats:sup>+<\/jats:sup>\n                      TILs compared to PBMCs, establishing the basis for preferential intra-tumoral targeting.\n                      <jats:italic>Ex-vivo<\/jats:italic>\n                      assays demonstrated that PD1-IL2v preferentially targets CD8\n                      <jats:sup>+<\/jats:sup>\n                      TIL subsets (stem-like and effector) over Tregs. This preferential targeting translated into superior biological activity, with PD1-IL2v inducing higher STAT5 phosphorylation (STAT5-P) in stem-like and effector CD8\n                      <jats:sup>+<\/jats:sup>\n                      T cells compared to Tregs, confirming the intended\n                      <jats:italic>cis<\/jats:italic>\n                      -targeting and enhanced IL-2R agonism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>These findings provide translational validation for PD1-IL2v\u2019s mechanism, demonstrating selective intra-tumoral immune stimulation while minimizing Treg activation. This characterization identifies PD-1 receptor density and subset prevalence as critical factors for drug activity and represents potentially useful biomarkers for predicting patient responsiveness and guiding patient selection.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1843841","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T05:24:30Z","timestamp":1780291470000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Target receptor expression dictates the selective intra-tumoral targeting of CD8+ T cells by eciskafusp alfa in matched PBMCs and TILs from CPI-na\u00efve patients"],"prefix":"10.3389","volume":"17","author":[{"given":"Amrita","family":"Manchala","sequence":"first","affiliation":[{"name":"Roche Pharma Research and Early Development, Roche Innovation Center Z\u00fcrich","place":["Schlieren, Switzerland"]},{"name":"Institute of Experimental 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