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. 2019 Aug 1;8(8):1168-1175.
doi: 10.1530/EC-19-0308.

PD-1 and PD-L1 expression in pulmonary carcinoid tumors and their association to tumor spread

Tiina Vesterinen  1   2 , Teijo Kuopio  3 , Maarit Ahtiainen  4 , Aija Knuuttila  5 , Harri Mustonen  6 , Kaisa Salmenkivi  1 , Johanna Arola  1 , Caj Haglund  6   7
Affiliations

PD-1 and PD-L1 expression in pulmonary carcinoid tumors and their association to tumor spread

Tiina Vesterinen et al. Endocr Connect. .

Abstract

Pulmonary carcinoid (PC) tumors are rare tumors that account for approximately 1% of all lung cancers. The primary treatment option is surgery, while there is no standard treatment for metastatic disease. As the number of PCs diagnosed yearly is increasing, there is a need to establish novel therapeutic options. This study aimed to investigate programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1) expression in PC tumors since blocking of the PD-1/PD-L1 pathway is a promising therapeutic option in various other malignancies. A total of 168 PC patients treated between 1990 and 2013 were collected from the Finnish biobanks. After re-evaluation of the tumors, 131 (78%) were classified as typical carcinoid (TC) and 37 (22%) as atypical carcinoid (AC) tumors. Primary tumor samples were immunohistochemically labeled for PD-1, PD-L1 and CD8. High PD-1 expression was detected in 16% of the tumors. PD-L1 expression was detected in 7% of TC tumors; all AC tumors were PD-L1 negative. PD-L1 expression was associated with mediastinal lymph-node metastasis at the time of diagnosis (P = 0.021) as well as overall metastatic potential of the tumor (P = 0.010). Neither PD-1 expression, PD-L1 expression nor CD8+ T cell density was associated with survival. In conclusion, PD-1 and PD-L1 were expressed in a small proportion of PC tumors and PD-L1 expression was associated with metastatic disease. Targeting of the PD-1/PD-L1 pathway with immune checkpoint inhibitors may thus offer a treatment option for a subset of PC patients.

Keywords: PD-1; PD-L1; immunohistochemistry; neuroendocrine tumor; pulmonary carcinoid tumor.

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Figures

Figure 1
Figure 1
Immunohistochemical images of programmed death ligand 1 (PD-L1), programmed death protein 1 (PD-1) and CD8 staining in pulmonary carcinoid tumors. Positive membranous staining of PD-L1 in a primary typical carcinoid (TC) tumor (A) and in corresponding lymph-node metastasis (B). Intratumoral lymphocytes expressing PD-1 in a TC tumor (C). A TC tumor with an abundant number of intratumoral CD8+ T cells (D). Scale bar 50 µm, original magnification 40×. Images obtained from digitized slides with CaseViewer software (3D HISTECH, Budapest, Hungary).
See this image and copyright information in PMC

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