CD8+/FOXP3+ ratio and PD-L1 expression associated with survival in pT3N0M0 stage esophageal squamous cell cancer.
Data describing relationships between the tumor immune microenvironment and patient outcome are limited for esophageal squamous cell cancer (ESCC). The present study investigated the prognostic values of programmed death-ligand 1 (PD-L1) expression and CD8+ or forkhead box protein 3+ (FOXP3+) tumor-infiltrating lymphocytes (TILs) in 133 pathological T3N0M0 stage ESCC patients who underwent radical resection without neoadjuvant or adjuvant therapy. CD8+ and FOXP3+ TIL densities as well as PD-L1 levels in tumor cells and lymphocytes, were assessed through immunohistochemical staining. Patient survival was not associated with CD8+ or FOXP3+ TILs alone, but PD-L1 expression and the CD8+/FOXP3+ ratio were independent predictors of both disease-free and overall survival. PD-L1 expression correlated with age (p = 0.029), tumor length (p < 0.001), tumor differentiation status (p = 0.002) and reduced intratumoral CD8+ TIL density (p < 0.001). Our results suggest pT3N0M0 ESCC clinical outcomes correlate with CD8+ and FOXP3+ TIL densities and PD-L1 levels. Moreover, an intrinsic mechanism for induction of PD-L1 overexpression may be occurring during early tumor oncogenesis. This information may be useful for stratifying patients and guide the application of checkpoint blockade therapy in ESCC.
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
Yingming
Y
Zhu
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
Minghuan
M
Li
Department of Pathology, Shandong Cancer Hospital and Institute, Shandong University Jinan, China.
Dianbin
D
Mu
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
Li
L
Kong
Department of Pathology, Shandong Cancer Hospital and Institute, Shandong University Jinan, China.
Jianbo
J
Zhang
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
Fen
F
Zhao
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
Zhenxiang
Z
Li
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
Xuemei
X
Liu
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
Cong
C
Bo
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong University, Jinan, China.
Jinming
J
Yu
D000328:Adult; D000368:Aged; D060890:B7-H1 Antigen / Q000032:analysis* / Q000502:physiology; D016827:CD8 Antigens / Q000032:analysis*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D004938:Esophageal Neoplasms / Q000276:immunology / Q000401:mortality* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D051858:Forkhead Transcription Factors / Q000032:analysis*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D059016:Tumor Microenvironment
D060890:B7-H1 Antigen; C423236:CD274 protein, human; D016827:CD8 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
CD8; esophageal squamous cell cancer; forkhead box protein 3; pT3N0M0; programmed death receptor ligand-1
Br J Cancer. 2008 Apr 8;98(7):1258-63
18349839
Lancet. 2016 May 7;387(10031):1909-20
26952546
Cancer Res. 2014 Feb 1;74(3):665-74
24336068
Nature. 2014 Nov 27;515(7528):568-71
25428505
N Engl J Med. 2012 Jun 28;366(26):2443-54
22658127
Oncotarget. 2016 Feb 16;7(7):7913-24
26761210
Neoplasia. 2006 Mar;8(3):190-8
16611412
Breast Cancer Res. 2015 Sep 04;17:124
26341640
Cancer Discov. 2016 Aug;6(8):811
27325283
J Pathol. 2014 Jan;232(2):199-209
24122236
Dis Esophagus. 2010 May;23(4):340-6
19788437
Nat Rev Immunol. 2008 Jul;8(7):523-32
18566595
Curr Opin Immunol. 2015 Apr;33:101-11
25728990
Br J Surg. 2016 Jun;103(7):845-54
26953091
Clin Cancer Res. 2005 Apr 15;11(8):2947-53
15837746
Oncotarget. 2015 Aug 28;6(25):20840-50
26369701
Cancer Med. 2013 Oct;2(5):662-73
24403232
Breast Cancer Res Treat. 2014 Jul;146(1):15-24
24842267
Biostatistics. 2009 Oct;10(4):603-20
19502615
Eur J Cancer. 2016 Jan;52:1-9
26623522
CA Cancer J Clin. 2015 Mar;65(2):87-108
25651787
Cancer Res. 2003 Apr 1;63(7):1555-9
12670904
J Clin Oncol. 2014 Apr 1;32(10):1020-30
24590637
Int J Clin Exp Pathol. 2014 Aug 15;7(9):6015-23
25337246
J Cancer Res Ther. 2015 Aug;11 Suppl 1:C16-23
26323918
J Exp Med. 2014 May 5;211(5):781-90
24778419
Oncotarget. 2016 Mar 22;7(12):15033-46
26930715
Oral Oncol. 2015 Mar;51(3):221-8
25500094
Ann Surg Oncol. 2010 Jul;17(7):1721-4
20369299
Oncoimmunology. 2015 Apr 02;4(3):e990800
25949908
Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18538-43
16344461
Cancer Immunol Immunother. 2007 Aug;56(8):1173-82
17186290
Cancer Res. 2015 Jun 1;75(11):2139-45
25977340
Sci Transl Med. 2012 Mar 28;4(127):127ra37
22461641
Oncoimmunology. 2015 Aug 31;5(3):e1086862
27141343
Oral Oncol. 2011 Dec;47(12):1148-53
21911310
N Engl J Med. 2012 Jun 28;366(26):2455-65
22658128