R ES E A R C H Open Access
Prognostic significance of PD-L1 expression
and CD8+ T cell infiltration in pulmonary
neuroendocrine tumors
Haiyue Wang
1†
, Zhongwu Li
1†
, Bin Dong
2
, Wei Sun
1
, Xin Yang
1
, Ruping Liu
3
, Lixin Zhou
1
, Xiaozheng Huang
1
,
Ling Jia
1
and Dongmei Lin
1*
Abstract
Background: Recent research suppo rts a significant role of immune checkpoint inh ibitors in the treatment of
solid tumors. However, relevant reports for programme d death-ligand 1 (PD-L1) and CD8+ tumor-infiltrating
lymphocytes (TILs) in pulmonary neuroendocrine tumors (PNETs) have not been fully studied. Therefore, we
investigated PNETs fo r the expression of PD-L1 and infiltration by CD8+ TILs as well as the prognostic value
of both factors.
Methods: In total, 159 specimens of P NETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included i n this study.
Immunohistochemistry (IHC) was used to detect the expression of PD-L1 in these cases. Cases demonstrating
≥5% tumor cell expression or any expression (> 1%) of PD-L1 on immune cells were considered positive. CD8
+ TILs both withi n s troma and tumor areas of invasive carcinoma were a nalyzed using whole-slide digital
imaging. Manual regio nal an notation and machine cell cou nts were performed fo r each case.
Results: Positive expression of PD-L1 was observed in 72 cases (45.3%), including 9 cases (5.7%) with
expression exclusively on tumor cells, 46 cases (28.9%) with expression exclusively on immune cells, and 17
cases (10.7%) with the expression on tumor cells and immune cells. PD-L1 expression w as a ssociated with
necrosis (p < 0.001), high pathologic grade (p < 0.001) and histologic type (p < 0.001). No correlation was
observed with overall survival (OS) (p = 0.158) or progression-free survival (PFS) (p = 0.315). In contrast, higher
CD8+ T cell density was a sso ciated with the absence of vascular invasion (p = 0.004), histologic type (p =0.005),
negative lymph node metastasis (p = 0.005) and lower clinical staging (p = 0.007). Moreover, multivariate
analysis revealed that CD8+ stromal TIL was an independent prognost ic factor for improved OS (p = 0.009)
and PFS (p = 0.002).
Conclusion: PD-L1 was expressed in approximately half of the PNETs. The majority of the expression was
observed in immune cells. Positive expression of PD-L1 showed no correlation with OS or PFS, while higher
CD8+ TILs within stroma was proved to be an independent prognostic factor for favorable OS and PFS of
PNETs.
Keywords: Pulmonary neuroendocrine tumor, PD-L1, CD8+ TILs
* Correspondence: lindm100142@163.com
†
Haiyue Wang and Zhongwu Li contributed equally to this work.
1
Key Laboratory of Carcinogenesis and Translational Research (Ministry of
Education), Department of Pathology, Peking University Cancer Hospital &
Institute, No. 52 Fucheng Road, Haidian District, Beijing 100142, People’s
Republic of China
Full list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0
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reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to
the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver
(http://creativecommons.org/publicdomain/zero/1.0/ ) applies to the data made available in this article, unless otherwise stated.
Wang et al. Diagnostic Pathology (2018) 13:30
https://doi.org/10.1186/s13000-018-0712-1