Programmed Cell Death Ligand (PD-L1) Expression in Stage II and III Lung Adenocarcinomas and Nodal Metastases.
Programmed death ligand 1 (PD-L1) expression determined by immunohistochemistry (IHC) may serve as a predictive biomarker for anti-PD-1/PD-L1 therapies; however, little is known about intertumoral heterogeneity of PD-L1 expression determined by IHC in lung adenocarcinomas (ADCs), and there have been conflicting results on the prognostic role of PD-L1 expression in ADCs.



PD-L1 expression was evaluated in resected stage II and III ADCs by using various cutoffs and correlated with clinicopathologic parameters and survival. PD-L1 expression was also compared between the primary tumor and lymph node metastases.



There were 109 study cases. PD-L1 expression was seen in 56 (51%), 43 (39%), and 19 (17%) when cutoffs of at least 1%, at least 5%, and at least 50%, respectively, were used. Abundant intratumoral CD8-positive T cells were a significant predictor of the expression in the primary tumor, with cutoffs of 1% and 5% (p < 0.001 for both) by multivariate analysis, whereas they were a nonsignificant predictor of the expression with a 50% cutoff (p = 0.076). PD-L1 expression was concordant between the primary tumor and nodal metastasis in most of the cases, but it was discrepant in up to 38%. The discrepancy was attributed in part to different predominant histologic patterns between the primary and metastatic tumors. In the entire cohort, PD-L1 expression with all cutoffs had no bearing on 5-year recurrence-free survival.



PD-L1 expression is associated with abundant intratumoral CD8-positive T cells in resected ADCs, suggesting a predictive role of PD-L1 expression in anti-PD-1/PD-L1 therapies; however, the possible intertumoral heterogeneity of PD-L1 expression raises a concern about selecting the most appropriate sample for PD-L1 IHC.
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Hironori
H
Uruga
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Emine
E
Bozkurtlar
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts.
Tiffany G
TG
Huynh
Cancer Center, Massachusetts General Hospital, Boston, Massachusetts.
Alona
A
Muzikansky
Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan.
Yasushi
Y
Goto
Cancer Center, Massachusetts General Hospital, Boston, Massachusetts.
Maria
M
Gomez-Caraballo
Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Aaron N
AN
Hata
Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Justin F
JF
Gainor
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Harvard Medical School, Boston, Massachusetts.
Eugene J
EJ
Mark
Cancer Center, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Jeffrey A
JA
Engelman
Division of Thoracic Surgery, Massachusetts General Hospital, Boston, Massachusetts; Department of Surgery, Harvard Medical School, Boston, Massachusetts.
Michael D
MD
Lanuti
Department of Pathology, Massachusetts General Hospital, Boston, Massachusetts; Department of Pathology, Harvard Medical School, Boston, Massachusetts. Electronic address: MMINOKENUDSON@partners.org.
Mari
M
Mino-Kenudson
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis; D060890:B7-H1 Antigen / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate
D060890:B7-H1 Antigen; D014408:Biomarkers, Tumor
Adjuvant therapy; Lung adenocarcinoma; Lymph node metastasis; PD-L1; Programmed death-ligand 1; Tumor-infiltrating lymphocyte