{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:14:03Z","timestamp":1790741643319,"version":"4.1.0"},"reference-count":34,"publisher":"BMJ","issue":"11","license":[{"start":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T00:00:00Z","timestamp":1637798400000},"content-version":"unspecified","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2021,11,2]]},"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>An elevated peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is a negative prognostic marker for patients with non-small cell lung cancer (NSCLC) receiving chemotherapy and immune checkpoint inhibitors. Whether dNLR is also associated with clinical outcomes to first-line pembrolizumab among patients with NSCLC and a programmed cell death ligand 1 (PD-L1) Tumor Proportion Score (TPS) of \u226550% is uncertain. How dNLR relates to the tumor immune microenvironment is also unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>In two participating academic centers, we retrospectively analyzed the dNLR (defined as the absolute neutrophil count\/white cell count \u2013 absolute neutrophil count) prior to initiation of first-line pembrolizumab in patients with metastatic NSCLC and a PD-L1 TPS \u226550%\u2009and lacking genomic alterations in <jats:italic>EGFR<\/jats:italic> and <jats:italic>ALK<\/jats:italic>. An unbiased recursive partitioning algorithm was used to investigate an optimal dNLR cut-off with respect to objective response rate (ORR). Multiplexed immunofluorescence for CD8+, FOXP3+, PD-1+, and PD-L1 was performed on a separate cohort of NSCLCs to determine the immunophenotype associated with dNLR.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A total of 221 patients treated with first-line pembrolizumab were included in this study. The optimal dNLR cut-off to differentiate treatment responders from non-responders was 2.6. Compared with patients with a dNLR \u22652.6 (n=97), patients with dNLR &lt;2.6 (n=124) had a significantly higher ORR (52.4% vs 24.7%, p&lt;0.001), a significantly longer median progression-free survival (mPFS 10.4 vs 3.4 months, HR 0.48, 95% CI 0.35 to 0.66, p&lt;0.001), and a significantly longer median overall survival (mOS 36.6 vs 9.8 months, HR 0.34, 95% CI 0.23 to 0.49, p&lt;0.001). After adjusting for age, sex, tobacco use, performance status, histology, serum albumin level, oncogenic driver status, and PD-L1 distribution (50%\u201389% vs \u226590%), a dNLR &lt;2.6 was confirmed to be an independent predictor of longer mPFS (HR 0.47, 95% CI 0.33 to 0.67, p&lt;0.001) and mOS (HR 0.32, 95% CI 0.21 to 0.49, p&lt;0.001). Among advanced NSCLC samples with a PD-L1 TPS of \u226550%, those with a dNLR &lt;2.6 had significantly higher numbers of tumor-associated CD8+, FOXP3+, PD-1 +immune cells, and PD-1 +CD8+T cells than those with a dNLR \u22652.6.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Among patients with NSCLC and a PD-L1 TPS \u226550%, a low dNLR has a distinct immune tumor microenvironment and more favorable outcomes to first-line pembrolizumab.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/jitc-2021-003536","type":"journal-article","created":{"date-parts":[[2021,11,25]],"date-time":"2021-11-25T11:31:35Z","timestamp":1637839895000},"page":"e003536","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":90,"title":["Low peripheral blood derived neutrophil-to-lymphocyte ratio (dNLR) is associated with increased tumor T-cell infiltration and favorable outcomes to first-line pembrolizumab in non-small cell lung cancer"],"prefix":"10.1136","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8072-5946","authenticated-orcid":false,"given":"Joao V","family":"Alessi","sequence":"first","affiliation":[{"name":"Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0651-2678","authenticated-orcid":false,"given":"Biagio","family":"Ricciuti","sequence":"additional","affiliation":[{"name":"Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie L","family":"Alden","sequence":"additional","affiliation":[{"name":"Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arrien A","family":"Bertram","sequence":"additional","affiliation":[{"name":"Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica J","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa","family":"Sakhi","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Nishino","sequence":"additional","affiliation":[{"name":"Department of Radiology, Brigham and Women\u2019s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor R","family":"Vaz","sequence":"additional","affiliation":[{"name":"Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Lindsay","sequence":"additional","affiliation":[{"name":"Knowledge Systems Group, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison M","family":"Turner","sequence":"additional","affiliation":[{"name":"ImmunoProfile, Brigham & Women\u2019s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Pfaff","sequence":"additional","affiliation":[{"name":"ImmunoProfile, Brigham & Women\u2019s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bijaya","family":"Sharma","sequence":"additional","affiliation":[{"name":"ImmunoProfile, Brigham & Women\u2019s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristen D","family":"Felt","sequence":"additional","affiliation":[{"name":"ImmunoProfile, Brigham & Women\u2019s Hospital and Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott J.","family":"Rodig","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham and Women\u2019s Hospital, Boston, Massachusetts, USA"},{"name":"Center for Immuno-Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin F.","family":"Gainor","sequence":"additional","affiliation":[{"name":"Department of Medicine, Massachusetts General Hospital Cancer Center, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0928-5244","authenticated-orcid":false,"given":"Mark M.","family":"Awad","sequence":"additional","affiliation":[{"name":"Lowe Center for Thoracic Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2021,11,25]]},"reference":[{"key":"2025100313212006000_9.11.e003536.1","doi-asserted-by":"crossref","unstructured":"Rosales C . 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