biostudies-literatureGeorge SLudwig Center at HarvardBroadIgniteHoward Hughes Medical InstituteAlexandra J. Miliotis Pediatric Oncology Research FundCatherine England Leiomyosarcoma Research FundHoward Hughes Medical Institute Medical Research FellowshipNCI NIH HHSErica Kaitz LMS RESEARCH NOW FundNIHBroadNext10197-204https://www.ebi.ac.uk/biostudies/studies/S-EPMC5408320biostudies-literatureUnknown46(2)Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance. Both tumors stained diffusely for PD-L2 and showed sparse PD-L1 staining. PD-1⁺ cell infiltration significantly decreased in the resistant tumor (p = 0.039). Genomically, the treatment-resistant tumor uniquely harbored biallelic PTEN loss and had reduced expression of two neoanImmunityLoss of PTEN Is Associated with Resistance to Anti-PD-1 Checkpoint Blockade Therapy in Metastatic Uterine Leiomyosarcoma.PMC5408320R01 CA155010P50CA101942K08CA188615P50 CA101942R01 CA140594K08 CA188615R50 CA211482Ott PAWong KKDemetri GDLipschitz MAmin-Mansour AHammerman PFreeman GJMiao DRaut CPAdeegbe DShukla SWu CJVan Allen EMGeorge SCarter SLRodig SJfalseLoss of PTEN Is Associated with Resistance to Anti-PD-1 Checkpoint Blockade Therapy in Metastatic Uterine Leiomyosarcoma.Response to immune checkpoint blockade in mesenchymal tumors is poorly characterized, but immunogenomic dissection of these cancers could inform immunotherapy mediators. We identified a treatment-naive patient who has metastatic uterine leiomyosarcoma and has experienced complete tumor remission for >2 years on anti-PD-1 (pembrolizumab) monotherapy. We analyzed the primary tumor, the sole treatment-resistant metastasis, and germline tissue to explore mechanisms of immunotherapy sensitivity and resistance. Both tumors stained diffusely for PD-L2 and showed sparse PD-L1 staining. PD-1⁺ cell infiltration significantly decreased in the resistant tumor (p = 0.039). Genomically, the treatment-resistant tumor uniquely harbored biallelic PTEN loss and had reduced expression of two neoan2017-01-01T00:00:00Z2017 Feb2026-05-30T08:34:59.453Z2019-03-26T23:03:13ZS-EPMC54083202822827910.1016/j.immuni.2017.02.001