title: Prognostic value of tumor-infiltrating lymphocytes for patients with completely resected stage IIIA(N2) non-small cell lung cancer.
abstract: BACKGROUND
  The patient prognosis after complete resection for pathologic stage IIIA(N2) non-small cell lung cancer (NSCLC) remains a significant concern. The clinical relevance of the host immune response to NSCLC has yet to be established. We aimed to investigate the prognostic value of tumor-infiltrating lymphocytes (TILs) in a uniform cohort of patients with completely resected stage IIIA(N2) NSCLC.
  
  
  METHODS
  From 2005 to 2012, consecutive patients with pathologic stage IIIA(N2) NSCLC who underwent complete resection at our institution were reviewed. For each case, full-face hematoxylin and eosin-stained sections from surgical specimens were evaluated for the TIL density. A published, recommended TIL scoring scale was followed. The patients were stratified into the TIL- or TIL+ group based on pathologic evaluation.
  
  
  RESULTS
  Data from 320 patients were included in the analysis. Based on a median follow-up duration of 30.8 months, a higher density of TILs was associated with an improved postoperative survival time (P = 0.06). Subgroup analyses indicated that this positive effect was the greatest for patients with squamous cell carcinoma (SCC; P = 0.03). Among those with SCC, the TIL+ patients experienced a significantly increased 3-year distant metastasis-free survival (DMFS) compared to the TIL- patients (60.6% versus 42.7%, P = 0.02). Multivariate analyses of the 93 patients with SCC tumors confirmed that TIL+ was an independent prognostic factor for an increased DMFS (HR = 0.39, 95%CI 0.17-0.87, P = 0.02) and a prolonged overall survival (OS; HR = 0.47, 95%CI 0.22-1.00, P = 0.05).
  
  
  CONCLUSIONS
  Our data suggest a potential role of TILs in predicting the survival of patients with completely resected stage IIIA(N2) NSCLC. The beneficial effects of TILs were more pronounced in the prediction of the DMFS and the OS in patients with SCC. This parameter should be considered for prospective inclusion in clinical trials.
authors.affiliation: Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.|Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Xu-Wei
authors.initials: XW
authors.lastname: Cai
authors.affiliation: Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Zheng-Fei
authors.initials: ZF
authors.lastname: Zhu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Jia-Qing
authors.initials: JQ
authors.lastname: Xiang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Ya-Wei
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: Department of Thoracic Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Hai-Quan
authors.initials: HQ
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.|Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Fu
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis*; D018287:Carcinoma, Large Cell / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000473:pathology* / Q000601:surgery; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor
keywords: lymphocytic infiltration; non-small cell lung cancer; prognosis; survival; tumor-infiltrating lymphocytes
references.citation: Br J Cancer. 2006 Jan 30;94(2):275-80
references.pmid: 16421594
references.citation: Cochrane Database Syst Rev. 2005;(2):CD002142
references.pmid: 15846628
references.citation: Science. 2006 Sep 29;313(5795):1960-4
references.pmid: 17008531
references.citation: Clin Cancer Res. 2008 Aug 15;14(16):5220-7
references.pmid: 18698040
references.citation: Int J Radiat Oncol Biol Phys. 2008 Nov 1;72(3):695-701
references.pmid: 18439766
references.citation: Ann Thorac Surg. 2009 Feb;87(2):365-71; discussion 371-2
references.pmid: 19161739
references.citation: Chest. 2009 Jul;136(1):260-71
references.pmid: 19584208
references.citation: Oncogene. 2010 Feb 25;29(8):1093-102
references.pmid: 19946335
references.citation: Lancet. 2010 Apr 10;375(9722):1267-77
references.pmid: 20338627
references.citation: Int J Radiat Oncol Biol Phys. 2010 Jun 1;77(2):321-8
references.pmid: 19775829
references.citation: Radiother Oncol. 2010 Jul;96(1):84-8
references.pmid: 20541823
references.citation: J Clin Oncol. 2011 Feb 20;29(6):610-8
references.pmid: 21245428
references.citation: Cell. 2011 Mar 4;144(5):646-74
references.pmid: 21376230
references.citation: J Surg Res. 2011 May 15;167(2):207-10
references.pmid: 19896677
references.citation: Oncologist. 2011;16(5):672-81
references.pmid: 21378080
references.citation: Oncologist. 2011;16(5):641-50
references.pmid: 21482587
references.citation: J Thorac Oncol. 2011 Apr;6(4):824-33
references.pmid: 21173711
references.citation: Br J Cancer. 2011 Jun 28;105(1):93-103
references.pmid: 21629244
references.citation: Clin Cancer Res. 2011 Aug 15;17(16):5247-56
references.pmid: 21659461
references.citation: Immunotherapy. 2011 Oct;3(10):1235-51
references.pmid: 21995574
references.citation: J Surg Res. 2011 Nov;171(1):1-5
references.pmid: 21571304
references.citation: Nat Rev Clin Oncol. 2011 Dec;8(12):711-9
references.pmid: 21826083
references.citation: Nat Rev Cancer. 2012 Apr;12(4):298-306
references.pmid: 22419253
references.citation: Int J Radiat Oncol Biol Phys. 2012 Jun 1;83(2):727-33
references.pmid: 22208965
references.citation: J Clin Oncol. 2012 Jun 10;30(17):2046-54
references.pmid: 22547592
references.citation: Ann Surg Oncol. 2012 Oct;19(11):3581-90
references.pmid: 22555345
references.citation: Ann Oncol. 2013 May;24(5):1170-9
references.pmid: 23393121
references.citation: Chest. 2013 May;143(5 Suppl):e314S-40S
references.pmid: 23649445
references.citation: Lung. 2013 Jun;191(3):265-70
references.pmid: 23494387
references.citation: J Clin Oncol. 2013 Nov 20;31(33):4252-9
references.pmid: 24127443
references.citation: J Pathol. 2014 Jan;232(2):199-209
references.pmid: 24122236
references.citation: Radiother Oncol. 2014 Jan;110(1):3-8
references.pmid: 24100149
references.citation: Int J Radiat Oncol Biol Phys. 2014 Apr 1;88(5):1100-7
references.pmid: 24529715
references.citation: Med Oncol. 2014 May;31(5):960
references.pmid: 24748366
references.citation: J Clin Oncol. 2014 Sep 20;32(27):2935-7
references.pmid: 25071115
references.citation: J Clin Oncol. 2014 Sep 20;32(27):2959-66
references.pmid: 25071121
references.citation: J Clin Oncol. 2015 Mar 10;33(8):870-6
references.pmid: 25667283
references.citation: BMC Cancer. 2015;15:348
references.pmid: 25934006
references.citation: Ann Oncol. 2015 Aug;26(8):1573-88
references.pmid: 25897013
references.citation: Tohoku J Exp Med. 2000 Jun;191(2):113-8
references.pmid: 10946920
references.citation: J Lab Clin Med. 2002 Nov;140(5):320-8
references.pmid: 12434133
references.citation: N Engl J Med. 2004 Jan 22;350(4):379-92
references.pmid: 14736930
references.citation: Cancer. 1989 Jan 15;63(2):309-16
references.pmid: 2535956
references.citation: Lung Cancer. 1993 Oct;10(1-2):13-9
references.pmid: 8069600
references.citation: J Clin Oncol. 2006 Jul 1;24(19):2998-3006
references.pmid: 16769986