Erna-Elise Paulsen1, Thomas K Kilvaer2, Mehrdad Rakaee Khanehkenari3, Samer Al-Saad4, Sigurd M Hald5, Sigve Andersen2, Elin Richardsen6, Nora Ness3, Lill-Tove Busund6, Roy M Bremnes2, Tom Donnem2. 1. Department of Oncology, University Hospital of North Norway, Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway. Electronic address: epa014@post.uit.no. 2. Department of Oncology, University Hospital of North Norway, Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway. 3. Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway. 4. Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway. 5. Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway. 6. Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Abstract
INTRODUCTION: Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non-small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC. MATERIALS AND METHODS: Tissue microarrays constructed from tumor tissue samples from 2 cohorts of a total of 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC. PD-L1 and PD-1 were evaluated by immunohistochemistry in the primary tumor and metastatic lymph node tissue. RESULTS: In univariate analysis, a high density of PD-L1+ immune cells in the stromal compartment (S-PD-L1) and PD-1+ intraepithelial tumor infiltrating lymphocytes (T-PD-1) was associated with favorable disease-specific survival (DSS; S-PD-L1, P = .004; T-PD-1, P = .012), both limited to the squamous cell carcinoma histologic subgroup (S-PD-L1, P = .002; T-PD-1, P = .034). A combined low S-PD-L1 and T-PD-1 was associated with poor survival in all patients (DSS: hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.37-2.40; P < .001) at both centers and for all pathologic stages. In multivariate analysis, S-PD-L1 and T-PD-1 were independent positive prognostic factors, and combined low scores remained an independent prognosticator for poor survival (DSS: HR, 1.72; 95% CI, 1.29-2.28; P < .001; disease-free survival, P = .001; overall survival, P = .005). CONCLUSION: Our study identified S-PD-L1 and T-PD-1 as independent positive prognostic factors for NSCLC patients. Their combination added significant prognostic impact within each pathologic stage and hence are feasible to include in a TNM Immunoscore.
INTRODUCTION: Immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) or its ligand, PD-L1, have gained momentum in the treatment of non-small cell lung cancer (NSCLC). However, their prognostic significance remains controversial. The present study evaluated the expression of PD-L1 and PD-1 and their potential role in an Immunoscore, supplementing the TNM classification of NSCLC. MATERIALS AND METHODS: Tissue microarrays constructed from tumor tissue samples from 2 cohorts of a total of 536 patients (University Hospital of North Norway, n = 285; Nordland Hospital, n = 251) with primary resected stage I to IIIA NSCLC. PD-L1 and PD-1 were evaluated by immunohistochemistry in the primary tumor and metastatic lymph node tissue. RESULTS: In univariate analysis, a high density of PD-L1+ immune cells in the stromal compartment (S-PD-L1) and PD-1+ intraepithelial tumor infiltrating lymphocytes (T-PD-1) was associated with favorable disease-specific survival (DSS; S-PD-L1, P = .004; T-PD-1, P = .012), both limited to the squamous cell carcinoma histologic subgroup (S-PD-L1, P = .002; T-PD-1, P = .034). A combined low S-PD-L1 and T-PD-1 was associated with poor survival in all patients (DSS: hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.37-2.40; P < .001) at both centers and for all pathologic stages. In multivariate analysis, S-PD-L1 and T-PD-1 were independent positive prognostic factors, and combined low scores remained an independent prognosticator for poor survival (DSS: HR, 1.72; 95% CI, 1.29-2.28; P < .001; disease-free survival, P = .001; overall survival, P = .005). CONCLUSION: Our study identified S-PD-L1 and T-PD-1 as independent positive prognostic factors for NSCLCpatients. Their combination added significant prognostic impact within each pathologic stage and hence are feasible to include in a TNM Immunoscore.
Authors: Siwen Hu-Lieskovan; Srabani Bhaumik; Kavita Dhodapkar; Jean-Charles J B Grivel; Sumati Gupta; Brent A Hanks; Sylvia Janetzki; Thomas O Kleen; Yoshinobu Koguchi; Amanda W Lund; Cristina Maccalli; Yolanda D Mahnke; Ruslan D Novosiadly; Senthamil R Selvan; Tasha Sims; Yingdong Zhao; Holden T Maecker Journal: J Immunother Cancer Date: 2020-12 Impact factor: 13.751
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