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Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma.
Oncotarget. 2017 May 02; 8(18):30175-30189.O

Abstract

Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in regulating the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating immune cells (TILs) in the tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Archival formalin-fixed, paraffin-embedded ESCC samples from treatment-naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy were collected between 2004 and 2014. Expression of PD-L1 in ESCC tumor specimens was assessed by immunohistochemistry (IHC), and the degree of TIL infiltration was evaluated by examining hematoxylin and eosin-stained (H&E) specimens. PD-L1+ as defined as ≥1% of tumor cell membranes showing ≥1+ intensity. In 428 patients, specimens from 341 (79.7%) were PD-L1+. In the definitive treatment group (patients who received curative esophagectomy or definitive [chemo-]radiation therapy), PD-L1 positivity was associated with a significantly shorter DFS and OS. In the palliative chemotherapy group exhibited, neither PFS nor OS correlated significantly with PD-L1 expression. PD-L1 expression was positively associated with TIL density. In 17 paired tumor tissues collected before and after treatment, an increase in PD-L1 expression was associated with disease progression, whereas a decrease in PD-L1 expression was associated with response to chemotherapy or disease control. So, PD-L1 expression was associated with a significantly worse prognosis in patients with ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients.

Authors+Show Affiliations

Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, P. R. China.Division of Anatomical Pathology, Department of Pathology & Clinical Biochemistry, Queen Mary Hospital, Hong Kong Special Administrative Region, P. R. China.Global Early Development, Merck Serono China, Beijing, P. R. China.Global Early Development, Merck Serono China, Beijing, P. R. China.Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, P. R. China.Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, P. R. China.Department of Gastrointestinal Oncology, Affiliated Hospital Cancer Center, Academy of Military Medical Sciences, Beijing, P. R. China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28404915

Citation

Jiang, Yubo, et al. "Prognostic Significance of Tumor-infiltrating Immune Cells and PD-L1 Expression in Esophageal Squamous Cell Carcinoma." Oncotarget, vol. 8, no. 18, 2017, pp. 30175-30189.
Jiang Y, Lo AWI, Wong A, et al. Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. Oncotarget. 2017;8(18):30175-30189.
Jiang, Y., Lo, A. W. I., Wong, A., Chen, W., Wang, Y., Lin, L., & Xu, J. (2017). Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. Oncotarget, 8(18), 30175-30189. https://doi.org/10.18632/oncotarget.15621
Jiang Y, et al. Prognostic Significance of Tumor-infiltrating Immune Cells and PD-L1 Expression in Esophageal Squamous Cell Carcinoma. Oncotarget. 2017 May 2;8(18):30175-30189. PubMed PMID: 28404915.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Prognostic significance of tumor-infiltrating immune cells and PD-L1 expression in esophageal squamous cell carcinoma. AU - Jiang,Yubo, AU - Lo,Anthony W I, AU - Wong,Angela, AU - Chen,Wenfeng, AU - Wang,Yan, AU - Lin,Li, AU - Xu,Jianming, PY - 2016/11/11/received PY - 2017/01/11/accepted PY - 2017/4/14/pubmed PY - 2018/3/6/medline PY - 2017/4/14/entrez KW - PD-L1 KW - TILs KW - esophageal squamous cell carcinoma KW - prognostic factor KW - tumor microenvironment SP - 30175 EP - 30189 JF - Oncotarget JO - Oncotarget VL - 8 IS - 18 N2 - Programmed death-1 receptor (PD-1) and its ligand (PD-L1) play an integral role in regulating the immune response against cancer. This study investigated the prognostic significance of PD-L1 expression on tumor cells and tumor-infiltrating immune cells (TILs) in the tumor microenvironment in Chinese patients with esophageal squamous cell carcinoma (ESCC). Archival formalin-fixed, paraffin-embedded ESCC samples from treatment-naïve patients with ESCC after surgery or by diagnostic endoscopic biopsy were collected between 2004 and 2014. Expression of PD-L1 in ESCC tumor specimens was assessed by immunohistochemistry (IHC), and the degree of TIL infiltration was evaluated by examining hematoxylin and eosin-stained (H&E) specimens. PD-L1+ as defined as ≥1% of tumor cell membranes showing ≥1+ intensity. In 428 patients, specimens from 341 (79.7%) were PD-L1+. In the definitive treatment group (patients who received curative esophagectomy or definitive [chemo-]radiation therapy), PD-L1 positivity was associated with a significantly shorter DFS and OS. In the palliative chemotherapy group exhibited, neither PFS nor OS correlated significantly with PD-L1 expression. PD-L1 expression was positively associated with TIL density. In 17 paired tumor tissues collected before and after treatment, an increase in PD-L1 expression was associated with disease progression, whereas a decrease in PD-L1 expression was associated with response to chemotherapy or disease control. So, PD-L1 expression was associated with a significantly worse prognosis in patients with ESCC. These observations suggest that PD-L1 may play a critical role in ESCC cancer progression and provide a rationale for developing PD-L1 inhibitors for treatment of a subset of ESCC patients. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/28404915/Prognostic_significance_of_tumor_infiltrating_immune_cells_and_PD_L1_expression_in_esophageal_squamous_cell_carcinoma_ L2 - https://www.oncotarget.com/lookup/doi/10.18632/oncotarget.15621 DB - PRIME DP - Unbound Medicine ER -