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Prognostic significance of PD-L1 expression and CD8+ T cell infiltration in pulmonary neuroendocrine tumors.
Diagn Pathol. 2018 May 22; 13(1):30.DP

Abstract

BACKGROUND

Recent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed 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 for 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 PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in 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 within stroma and tumor areas of invasive carcinoma were analyzed using whole-slide digital imaging. Manual regional annotation and machine cell counts were performed for 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 was associated 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 associated 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 prognostic 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.

Authors+Show Affiliations

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.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.Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Central Laboratory, Peking University Cancer Hospital & Institute, Beijing, 100142, People's Republic of China.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.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.Beijing Institute of Graphic Communication, Beijing, 102600, People's Republic of China.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.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.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.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. lindm100142@163.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29789013

Citation

Wang, Haiyue, et al. "Prognostic Significance of PD-L1 Expression and CD8+ T Cell Infiltration in Pulmonary Neuroendocrine Tumors." Diagnostic Pathology, vol. 13, no. 1, 2018, p. 30.
Wang H, Li Z, Dong B, et al. Prognostic significance of PD-L1 expression and CD8+ T cell infiltration in pulmonary neuroendocrine tumors. Diagn Pathol. 2018;13(1):30.
Wang, H., Li, Z., Dong, B., Sun, W., Yang, X., Liu, R., Zhou, L., Huang, X., Jia, L., & Lin, D. (2018). Prognostic significance of PD-L1 expression and CD8+ T cell infiltration in pulmonary neuroendocrine tumors. Diagnostic Pathology, 13(1), 30. https://doi.org/10.1186/s13000-018-0712-1
Wang H, et al. Prognostic Significance of PD-L1 Expression and CD8+ T Cell Infiltration in Pulmonary Neuroendocrine Tumors. Diagn Pathol. 2018 May 22;13(1):30. PubMed PMID: 29789013.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prognostic significance of PD-L1 expression and CD8+ T cell infiltration in pulmonary neuroendocrine tumors. AU - Wang,Haiyue, AU - Li,Zhongwu, AU - Dong,Bin, AU - Sun,Wei, AU - Yang,Xin, AU - Liu,Ruping, AU - Zhou,Lixin, AU - Huang,Xiaozheng, AU - Jia,Ling, AU - Lin,Dongmei, Y1 - 2018/05/22/ PY - 2018/01/10/received PY - 2018/05/13/accepted PY - 2018/5/24/entrez PY - 2018/5/24/pubmed PY - 2018/10/3/medline KW - CD8+ TILs KW - Pulmonary neuroendocrine tumor, PD-L1 SP - 30 EP - 30 JF - Diagnostic pathology JO - Diagn Pathol VL - 13 IS - 1 N2 - BACKGROUND: Recent research supports a significant role of immune checkpoint inhibitors in the treatment of solid tumors. However, relevant reports for programmed 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 for 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 PNETs (35 TC, 2 AC, 28 LCNEC, 94 SCLC) were included in 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 within stroma and tumor areas of invasive carcinoma were analyzed using whole-slide digital imaging. Manual regional annotation and machine cell counts were performed for 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 was associated 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 associated 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 prognostic 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. SN - 1746-1596 UR - https://www.unboundmedicine.com/medline/citation/29789013/Prognostic_significance_of_PD_L1_expression_and_CD8+_T_cell_infiltration_in_pulmonary_neuroendocrine_tumors_ L2 - https://diagnosticpathology.biomedcentral.com/articles/10.1186/s13000-018-0712-1 DB - PRIME DP - Unbound Medicine ER -