{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T13:30:41Z","timestamp":1788874241977,"version":"build-2803163510"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"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>Background<\/jats:title>\n                    <jats:p>CTLA-4\/CD80 and PD-1\/PD-L1 immune checkpoint pathways play critical roles in regulating T-cell activity within the tumor microenvironment (TME) of non-small cell lung cancer (NSCLC). While immune checkpoint inhibitors (ICIs) targeting PD-1\/PD-L1 have improved survival outcomes, response rates vary, and predictive biomarkers\u2019 alternative to PD-L1 expression are imperative. Our study aimed to identify PD-1\/PD-L1 and CTLA-4\/CD80 interaction states as enhanced predictive biomarkers for patient stratification to anti-PD-1\/PD-L1 therapies in NSCLC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study utilized the QF-Pro\n                      <jats:sup>\u00ae<\/jats:sup>\n                      platform to quantify CTLA-4\/CD80 and PD-1\/PD-L1 interaction states in formalin-fixed paraffin-embedded (FFPE) samples from a cohort of 67 NSCLC patients treated with anti-PD-1\/PD-L1 therapies. Corroborating prior findings, high PD-1\/PD-L1 interaction, measured by FRET efficiency, predicts improved response rates via overall survival (OS) and progression-free survival (PFS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Remarkably, we also identified high CTLA-4\/CD80 interaction (FRET efficiency \u22656.41%) as correlating with improved OS and PFS in response to anti-PD-1\/PD-L1 therapies. Patients with concurrently high PD-1\/PD-L1 and CTLA-4\/CD80 interactions exhibited the highest response rates, suggesting synergistic interplay between these checkpoints. In contrast, neither biomarker predicted response to chemotherapy in a separate cohort of 51 lung adenocarcinoma patients, confirming specificity for ICI therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These results highlight the potential of QF-Pro\n                      <jats:sup>\u00ae<\/jats:sup>\n                      as a robust tool for stratifying NSCLC patients for ICI treatment and underscore the clinical relevance of CTLA-4\/CD80 interaction as a predictive biomarker, paving the way for personalized immunotherapy strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1783685","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T10:51:50Z","timestamp":1784199110000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Immune checkpoint crosstalk: CTLA-4\/CD80 engagement as a predictor of anti-PD-1\/PD-L1 therapy outcome in NSCLC"],"prefix":"10.3389","volume":"17","author":[{"given":"Juan","family":"Gumuzio","sequence":"first","affiliation":[{"name":"HAWK Biosystems (formerly known as FASTBASE Solutions S.L.)","place":["Derio, Bizkaia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Miles","sequence":"additional","affiliation":[{"name":"HAWK Biosystems (formerly known as FASTBASE Solutions S.L.)","place":["Derio, Bizkaia, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Quimi","sequence":"additional","affiliation":[{"name":"HAWK 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