Assessing PDL-1 and PD-1 in Non-Small Cell Lung Cancer: A Novel Immunoscore Approach.
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.



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.



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).



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.
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.
Erna-Elise
EE
Paulsen
Department of Oncology, University Hospital of North Norway, Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
Thomas K
TK
Kilvaer
Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
Mehrdad Rakaee
MR
Khanehkenari
Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Samer
S
Al-Saad
Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
Sigurd M
SM
Hald
Department of Oncology, University Hospital of North Norway, Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
Sigve
S
Andersen
Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Elin
E
Richardsen
Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway.
Nora
N
Ness
Department of Medical Biology, UiT The Arctic University of Norway, Tromso, Norway; Department of Clinical Pathology, University Hospital of North Norway, Tromso, Norway.
Lill-Tove
LT
Busund
Department of Oncology, University Hospital of North Norway, Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
Roy M
RM
Bremnes
Department of Oncology, University Hospital of North Norway, Tromso, Norway; Department of Clinical Medicine, UiT The Arctic University of Norway, Tromso, Norway.
Tom
T
Donnem
D000230:Adenocarcinoma / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000936:Antigen-Antibody Complex / Q000276:immunology*; D060890:B7-H1 Antigen / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000378:metabolism / Q000556:secondary; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D061026:Programmed Cell Death 1 Receptor / Q000276:immunology / Q000378:metabolism*; D012189:Retrospective Studies; D015996:Survival Rate; D046888:Tissue Array Analysis
D000936:Antigen-Antibody Complex; D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor; C423236:CD274 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor
Immune checkpoints; Lymph node metastasis; PD; Prognostic; TNM stage I