Predictive clinical outcome of the intratumoral CD66b-positive neutrophil-to-CD8-positive T-cell ratio in patients with resectable nonsmall cell lung cancer.

The role of the interaction between tumor cells and inflammatory cells in nonsmall cell lung carcinoma (NSCLC) is unclear. In this study, the authors assessed the prognostic impact of intratumoral cluster of differentiation 66b (carcinoembryonic antigen-related cell adhesion molecule 8 [CD66b])-positive neutrophils and of the intratumoral CD66b-positive neutrophil-to-cluster of differentiation 8 (cell surface antigen T8 [CD8])-positive lymphocytes (the CD66b-positive neutrophil-to-CD8-positive lymphocyte ratio [iNTR]) in patients with resectable NSCLC. Expression levels of CD66b and CD8 were evaluated by immunohistochemistry on tissue microarrays consisting of 632 NSCLC specimens from patients who underwent curative surgery. The relation between clinicopathologic variables and patient outcome was assessed. Intratumoral CD66b-positive neutrophils were elevated in 318 patients (50%). In univariate analysis, an increase in CD66b-positive cells was associated with a high cumulative incidence of relapse (CIR) (median CIR, 51 months for low CD66b-positive cell density; 36 months for high CD66b-positive cell density; P = .002) and trended toward worse overall survival (OS) (median OS, 57 months for low CD66b-positive cell density; 54 months for high CD66b-positive cell density; P = .088). The iNTR was elevated in 190 patients (30%). An increased iNTR was strongly associated with both a high CIR (median CIR: 43 months for an iNTR ≤1; 34 months for an iNTR >1; P < .0001) and poor OS (median OS: 60 months for an iNTR ≤1; 46 months for an iNTR >1; P < .0001). In multivariate analysis, independent prognostic factors for a higher CIR were high iNTR (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.56-0.90; P = .005) and tumor stage >I, (HR, 0.39; 95% CI, 0.30-0.52; P < .0001). Independent prognostic factors for worse OS were a high iNTR (HR, 0.70; 95% CI, 0.54-0.91; P = .007) and tumor stage >I (HR, 0.35; 95% CI, 0.26-0.47; P < .0001). The current results indicated that the iNTR is a novel, independent prognostic factor for a high rate of disease recurrence and poor OS in patients with resectable NSCLC.

Ilie M ，Hofman V ，Ortholan C ，Bonnetaud C ，Coëlle C ，Mouroux J ，Hofman P ... -  《-》

Intratumoral neutrophils: a poor prognostic factor for hepatocellular carcinoma following resection.

Neutrophil infiltration has been linked to clinical outcome of various cancer types. However, its role in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated prognostic values for intratumoral and peritumoral neutrophils in HCC patients undergoing curative resection. The expression of CD66b, CD8, TGF-beta, and CD34 was assessed by immunohistochemistry in tissue microarrays containing paired intratumoral and peritumoral tissues from 197 patients receiving curative resection for HCC. Prognostic values for these and other clinicopathologic factors were evaluated. Intratumoral CD66b(+) neutrophils significantly correlated with CD8(+) T cells (r=0.240, p=0.004), TGF-beta expression (p=0.012), BCLC stage (p=0.016), and early recurrence (p=0.041). Increased intratumoral neutrophils were significantly associated with decreased RFS/OS (p=0.001 and p<0.001, respectively) in univariate analysis and were identified as an independent prognostic factor (HR=1.845, 95% CI=1.169-2.911, p=0.008 for RFS; HR=2.578, 95% CI=1.618-4.106, p<0.001 for OS) in multivariate analysis. Intratumoral neutrophil-to-CD8(+) T cell ratio (iNTR) better predicted the outcome in terms of minimum p values. Intratumoral neutrophils were also demonstrated to be statistically predictive for RFS/OS in the normal AFP subgroup, small HCC subgroup, and validation cohort. However, peritumoral neutrophils were not associated with the outcome of HCC. The presence of intratumoral neutrophils was a poor prognostic factor for HCC after resection. Intratumoral neutrophil-to-CD8(+) T cell ratio was a better predictor of outcome.

Li YW ，Qiu SJ ，Fan J ，Zhou J ，Gao Q ，Xiao YS ，Xu YF ... -  《-》

Tumor-associated neutrophils and macrophages in non-small cell lung cancer: no immediate impact on patient outcome.

A tumor-promoting impact of neutrophils and macrophages has been demonstrated in some cancers. However, the prognostic significance of innate immune cells in patients with non-small cell lung cancer (NSCLC) is unclear. A total of 335 consecutive patients resected for stage I-IIIA NSCLC were assessed for CD66b(+) neutrophils and CD163(+) macrophages in the tumor nests and adjacent stromal tissue by immunohistochemistry in whole tissue sections using stereology as well as automatic computerized quantification. Findings were correlated with clinical and histopathological parameters, baseline blood inflammatory markers (C-reactive protein (CRP) and white blood cell count (WBC)). Endpoints were recurrence-free survival (RFS) and overall survival (OS). Elevated CRP above median (101 nmol/l) and WBC above median (8.6 × 10(9)cells/l) were associated with poor RFS (p ≤ 0.002) and poor OS (p ≤ 0.01). Higher density of CD66b(+) in tumor nests and stroma was associated with elevated CRP and WBC, squamous cell histology, tumor size, and necrosis (p ≤ 0.01). Higher density of CD163(+) macrophages in tumor nests and stroma was associated with elevated CRP and lymph node metastases (p ≤ 0.049). The densities of tumor nest CD66b(+) neutrophils and CD163(+) macrophages were not significantly correlated with RFS or OS, irrespective of assessment method. The densities of tumor-associated CD66b(+) neutrophils and CD163(+) macrophages in NSCLC were correlated with adverse prognostic factors and systemic blood inflammation markers, but not directly correlated with RFS or OS. Further research of chronic inflammation in NSCLC is warranted.

Carus A ，Ladekarl M ，Hager H ，Pilegaard H ，Nielsen PS ，Donskov F ... -  《-》

Presence of intratumoral neutrophils is an independent prognostic factor in localized renal cell carcinoma.

Jensen HK ，Donskov F ，Marcussen N ，Nordsmark M ，Lundbeck F ，von der Maase H ... -  《-》

Association of immunoreactive hepatocyte growth factor with poor survival in resectable non-small cell lung cancer.

Siegfried JM ，Weissfeld LA ，Singh-Kaw P ，Weyant RJ ，Testa JR ，Landreneau RJ ... -  《CANCER RESEARCH》