Sigurd M Hald1, Mehrdad Rakaee2, Inigo Martinez2, Elin Richardsen3, Samer Al-Saad3, Erna-Elise Paulsen4, Egil Støre Blix4, Thomas Kilvaer4, Sigve Andersen4, Lill-Tove Busund3, Roy M Bremnes4, Tom Donnem4. 1. Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway. Electronic address: sigurd.hald@uit.no. 2. Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway. 3. Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway; Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway. 4. Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway; Department of Oncology, University Hospital of North Norway, Tromso, Norway.
Abstract
BACKGROUND: Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint receptor and a putative therapeutic target in non-small-cell lung cancer (NSCLC). We explored the prognostic effect of LAG-3+ tumor-infiltrating lymphocytes (TILs) in primary tumors and metastatic lymph nodes in NSCLC and its potential for inclusion in an immunoscore, supplementing the TNM classification. MATERIALS AND METHODS: Primary tumor tissue from 553 stage I-IIIB NSCLC patients and 143 corresponding metastatic lymph nodes were collected. The expression of LAG-3 was evaluated by immunohistochemistry on tissue microarrays. RESULTS: On univariate analysis, LAG-3+ TILs in the intraepithelial and stromal compartments of primary tumors and in the intraepithelial and extraepithelial compartments of metastatic lymph nodes were associated with improved disease-specific survival (DSS). On multivariate analysis, stromal LAG-3+ TILs were a significant independent predictor of improved DSS (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.43-0.82; P = .002). Stromal LAG-3+ TILs did not have prognostic impact across all pathologic stages. In the metastatic lymph nodes, intraepithelial (HR, 0.61; 95% CI, 0.38-0.99; P = .049) and extraepithelial (HR, 0.54; 95% CI, 0.29-0.70; P < .001) LAG-3+ TILs were independently associated with favorable DSS. CONCLUSION: LAG-3+ TILs are an independent positive prognostic factor in stage I-IIIB NSCLC. LAG-3 in metastatic lymph nodes is a candidate marker for an immunoscore in NSCLC.
BACKGROUND:Lymphocyte activation gene-3 (LAG-3) is an immune checkpoint receptor and a putative therapeutic target in non-small-cell lung cancer (NSCLC). We explored the prognostic effect of LAG-3+ tumor-infiltrating lymphocytes (TILs) in primary tumors and metastatic lymph nodes in NSCLC and its potential for inclusion in an immunoscore, supplementing the TNM classification. MATERIALS AND METHODS: Primary tumor tissue from 553 stage I-IIIB NSCLCpatients and 143 corresponding metastatic lymph nodes were collected. The expression of LAG-3 was evaluated by immunohistochemistry on tissue microarrays. RESULTS: On univariate analysis, LAG-3+ TILs in the intraepithelial and stromal compartments of primary tumors and in the intraepithelial and extraepithelial compartments of metastatic lymph nodes were associated with improved disease-specific survival (DSS). On multivariate analysis, stromal LAG-3+ TILs were a significant independent predictor of improved DSS (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.43-0.82; P = .002). Stromal LAG-3+ TILs did not have prognostic impact across all pathologic stages. In the metastatic lymph nodes, intraepithelial (HR, 0.61; 95% CI, 0.38-0.99; P = .049) and extraepithelial (HR, 0.54; 95% CI, 0.29-0.70; P < .001) LAG-3+ TILs were independently associated with favorable DSS. CONCLUSION:LAG-3+ TILs are an independent positive prognostic factor in stage I-IIIB NSCLC. LAG-3 in metastatic lymph nodes is a candidate marker for an immunoscore in NSCLC.
Authors: Mari Mino-Kenudson; Yin P Hung; Daniel J Shepherd; Elisabeth S Tabb; Keiko Kunitoki; M Lisa Zhang; Marina Kem; Jaimie Barth; David A Qualls; Meghan J Mooradian; Justin F Gainor Journal: Mod Pathol Date: 2021-12-08 Impact factor: 8.209
Authors: Scott Moerdler; Michelle Ewart; Debra L Friedman; Kara Kelly; Qinglin Pei; Mou Peng; XingXing Zang; Peter D Cole Journal: Leuk Lymphoma Date: 2020-10-28