Prognostic Impact of Immune Microenvironment in Lung Squamous Cell Carcinoma: Tumor-Infiltrating CD10+ Neutrophil/CD20+ Lymphocyte Ratio as an Independent Prognostic Factor.
BACKGROUND
We previously reported the prognostic significance of the lung adenocarcinoma immune microenvironment. In this study, we preformed comprehensive analysis of immune markers and their associations with prognosis in patients with lung squamous cell carcinoma.


METHODS
We reviewed surgically resected, solitary lung squamous cell carcinoma patients (n = 485; 1999-2009) who were randomly split into a training cohort (n = 331) and validation cohort (n = 154). We constructed tissue microarrays and performed immunostaining for CD3, CD45RO, CD8, CD4, FoxP3, CD20, CD68, CXCL12, CXCR4, CCR7, interleukin-7 receptor, and interleukin-12 receptor β2. Overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model.


RESULTS
Analysis of single immune cell infiltration revealed that high tumor-infiltrating CD10(+) neutrophils were associated with worse prognoses in the training cohort (p = 0.021). Analysis of biologically relevant immune cell combinations identified that patients with high CD10 neutrophil and low CD20(+) lymphocyte had a significantly worse OS (5-year OS, 42%) than those with other combinations of CD10 and CD20 (5-year OS, 62%; p < 0.001); this was confirmed in the validation cohort (p = 0.032). For the multivariate analysis, high CD10/low CD20 immune cell infiltration was an independent predictor of OS in both the training cohort (hazard ratio = 1.61, p = 0.006) and the validation cohort (hazard ratio = 1.75; p = 0.043).


CONCLUSIONS
High CD10(+)/low CD20(+) immune cell infiltration ratio is a significant prognostic factor of lung squamous cell carcinoma. Immunomodulatory therapy of tumor-specific neutrophil and B-lymphocyte responses may have applicability in the treatment of lung squamous cell carcinoma.
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York; Faculty of Medicine, Department of Diagnostic Pathology, Kagawa University, Kagawa, Japan.
Kyuichi
K
Kadota
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Department of Thoracic Surgery, University of Tokyo, Tokyo, Japan.
Jun-Ichi
JI
Nitadori
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Hideki
H
Ujiie
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
Daniel H
DH
Buitrago
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Kaitlin M
KM
Woo
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, New York.
Camelia S
CS
Sima
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York.
William D
WD
Travis
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York.
David R
DR
Jones
Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, New York. Electronic address: adusumip@mskcc.org.
Prasad S
PS
Adusumilli
D015703:Antigens, CD / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology* / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000378:metabolism*; D011379:Prognosis; D012189:Retrospective Studies; D059016:Tumor Microenvironment / Q000276:immunology*
D015703:Antigens, CD