Programmed death-1 ligand 1 and 2 are highly expressed in pleomorphic carcinomas of the lung: Comparison of sarcomatous and carcinomatous areas.
Pleomorphic carcinoma (PC) of the lung is a rare type of poorly differentiated non-small cell lung carcinoma (NSCLC) that belongs to sarcomatoid carcinoma (SC). It exhibits aggressive behaviour and resistance to chemotherapy and radiotherapy. Recently, immunotherapy targeting the programmed death-1 (PD-1)/PD ligand 1 (PD-L1) pathway has demonstrated favourable clinical outcomes in NSCLC. However, the expression patterns of PD-1-related molecules in pulmonary PC remain elusive. PD-L1 and PD-L2 expression was estimated in 41 cases of PC using immunohistochemistry. CD8(+) and PD-1(+) tumour-infiltrating lymphocytes (TILs) were also evaluated. PD-L1 and PD-L2 were highly expressed in pulmonary PCs (90.2% [37/41)]; 87.8% [36/41]). The amount of CD8(+) or PD-1(+) TILs and the ratio of PD-1(+)/CD8(+) TILs in PC were higher in males, smokers and older patients. PD-L1-positive PCs were infiltrated by higher numbers of CD8(+) TILs compared to PD-L1-negative cases (P=0.006). Of note, PD-L1 expression in pulmonary PCs was significantly higher in sarcomatous areas than in the carcinomatous portion (P=0.006). PC patients with a high ratio of PD-1(+)/CD8(+) TILs showed a shorter progression-free survival (P=0.036), whereas PD-L1 and PD-L2 expression had no prognostic implications. Our study demonstrates that pulmonary PCs very frequently express PD-L1 and PD-L2. Moreover, their expression is higher in sarcomatous cells than in carcinomatous areas. Thus, targeting the PD-1/PD-L1 pathway may represent a potential therapeutic candidate for this aggressive tumour.
Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Sehui
S
Kim
Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea.
Moon-Young
MY
Kim
Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea.
Jaemoon
J
Koh
Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Heounjeong
H
Go
Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Molecular Medicine and Biopharmaceutical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
Dong Soo
DS
Lee
Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: junarplus@chol.com.
Yoon Kyung
YK
Jeon
Department of Pathology, Seoul National University Hospital, Seoul, Republic of Korea; Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: doohyun@snu.ac.kr.
Doo Hyun
DH
Chung
D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000096:biosynthesis*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D012509:Sarcoma / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction; D046888:Tissue Array Analysis
D060890:B7-H1 Antigen; C423236:CD274 protein, human; C105992:PDCD1 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein; D061026:Programmed Cell Death 1 Receptor
Cancer immunotherapy; Pleomorphic carcinoma of the lung; Programmed death-1; Programmed death-1 ligand 1; Sarcomatoid carcinoma of the lung