{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:37:10Z","timestamp":1787017030409,"version":"build-2736575974"},"reference-count":31,"publisher":"BMJ","issue":"6","license":[{"start":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T00:00:00Z","timestamp":1782086400000},"content-version":"unspecified","delay-in-days":21,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2026,5,5]]},"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>Liver metastases (LMs) confer resistance to immune checkpoint blockade in advanced non-squamous non\u2010small cell lung cancer (ns\u2010NSCLC), likely through an immunosuppressive tumor microenvironment (TME). We hypothesized that vascular endothelial growth factor (VEGF)-A blockade, by remodeling the immunosuppressive TME, could restore the benefit of chemoimmunotherapy in LM+ patients. Here, we report the first comparative analysis of chemoimmunotherapy with and without bevacizumab specifically in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental design<\/jats:title>\n                    <jats:p>Data were analyzed from the phase III IMpower130 and IMpower150 trials in treatment\u2010na\u00efve, EGFR\/ALK-wild\u2010type patients with ns\u2010NSCLC. Treatment arms included chemotherapy (CT), CT plus atezolizumab (CT+immunotherapy (IT)), CT plus bevacizumab (CT+antiangiogenic (AA)), and CT+IT+\u2009AA, with LM as a stratification factor. Survival outcomes were assessed by Kaplan-Meier estimates and multivariate Cox regression analyses. Bulk and single\u2010cell RNA sequencing data were used to characterize the LM TME.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among 1,713 patients, 236 (13.8%) presented with LMs. In IMpower130, LM+ patients derived no overall survival (OS) benefit from CT plus IT (CT+IT) compared with CT alone (HR for OS: 1.05; 95% CI 0.63 to 1.73). In contrast, in IMpower150, the addition of bevacizumab to CT+IT (CT+IT+\u2009AA) significantly improved progression-free survival (PFS; HR: 0.49) and OS (HR: 0.52) in LM+ patients\u2014an effect not observed in patients without LM. Baseline transcriptomic exploratory analyses from IMpower150 revealed a myeloid-enriched, lymphocyte-depleted TME. Single-cell RNA sequencing further demonstrated VEGF-A\/VEGFR-1\/2 crosstalk between macrophages and endothelial cells, as well as an autocrine VEGF-A\/VEGFR-1 loop within macrophages.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The addition of bevacizumab to chemoimmunotherapy was associated with improved survival in ns\u2010NSCLC specifically in patients with LMs. These hypothesis-generating findings suggest that the benefit may stem from disruption of VEGF-A-driven immunosuppressive signaling in the liver, but require prospective confirmation.<\/jats:p>\n                  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France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Severine","family":"Mouraud","sequence":"additional","affiliation":[{"name":"Laboratoire de Recherche Translationnelle en Immunoth\u00e9rapies (LRTI), INSERM U1015, Gustave Roussy, Villejuif, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christophe","family":"Massard","sequence":"additional","affiliation":[{"name":"Drug Development Department, Gustave Roussy, Villejuif, Paris"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Besse","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Gustave Roussy, Villejuif, \u00cele-de-France, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yohann","family":"Loriot","sequence":"additional","affiliation":[{"name":"Drug Development Department, Gustave Roussy, Villejuif, Paris"},{"name":"Medical Oncology Department, Gustave Roussy, Villejuif, 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