title: Relationship between expression of PD-L1 and PD-L2 on esophageal squamous cell carcinoma and the antitumor effects of CD8⁺ T cells.
abstract: The programmed death-1 (PD-1)/programmed death-ligands (PD-Ls) signal pathway has been implicated as a potential immune escape mechanism in several human cancers. However, the studies of PD‑1/PD‑Ls pathway in esophageal squamous cell carcinoma (ECSS) are not yet sufficient. The current study investigated the expression of PD‑L1, PD‑L2 and PD‑1 in ESCC tissues. The correlations between the expression of these proteins and clinical histopathological parameters were analyzed. Then the stable transfected Ec109 cell lines overexpressing PD‑L1/PD‑L2 were established by plasmid transfection successfully. Ec109 and CD8+ T cells were co‑cultured to analyze the effects of PD‑1/PD‑Ls signal pathway on the function of CD8+ T cells including proliferation, apoptosis and interferon‑γ production. We found that PD‑L1-positive patients had significantly poorer prognosis than the negative patients, while their prognosis was not related to PD‑L2 expression. The count of PD‑1+ TILs (tumor‑infiltrating lymphocytes) was negatively correlated with both PD‑L1 and PD‑L2 expression. In functional studies, we found that PD‑1/PD‑Ls signal pathway was able to downregulate the function of CD8+ T lymphocyte and its function could be restored by blocking the signal pathway. This indicates that PD‑1/PD‑Ls may prevent effective antitumor immunity, which provides important evidence to delineate the cellular immune deficiency mechanism in ESCC. Therefore, PD-1/PD-Ls are predicted to become novel targets for ESCC immunotherapy.
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Changsen
authors.initials: C
authors.lastname: Leng
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Yin
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Qin
authors.affiliation: The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Xianben
authors.initials: X
authors.lastname: Liu
authors.affiliation: The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Haibo
authors.initials: H
authors.lastname: Sun
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Zongfei
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Xionghuai
authors.initials: X
authors.lastname: Hua
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Haomiao
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Thoracic Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
authors.forename: Junwei
authors.initials: J
authors.lastname: Zhu
authors.affiliation: The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450014, P.R. China.
authors.forename: Qiuming
authors.initials: Q
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D060890:B7-H1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002469:Cell Separation; D018920:Coculture Techniques; D004938:Esophageal Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D061027:Programmed Cell Death 1 Ligand 2 Protein / Q000096:biosynthesis* / Q000276:immunology; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D019139:Tumor Escape / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; C423236:CD274 protein, human; C556977:PDCD1LG2 protein, human; D061027:Programmed Cell Death 1 Ligand 2 Protein