Effect of pattern of lymphocyte infiltration in NSCLC on outcome

Journal of Clinical Oncology(2016)

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摘要
11079 Background: The role played by the immune system in determining survival in non-small-cell lung cancer (NSCLC) is unclear. The aim of this study was to investigate the prognostic significance of T-lymphocyte infiltration in NSCLC focusing on CD3+, cytotoxic CD8+ and FOXP3+ T regulatory (Treg) cells. Methods: Immunohistochemistry was used to detect CD3+, CD8+ and FOXP3+ lymphocytes in the tumor islets and tumor stroma in 186 patients with surgically resected NSCLC with a minimum follow-up of 3 years. Quantification of immune infiltration was performed using the Aperio automated image analysis system incorporating the Genie software tool. The median of tumor:stroma CD3+, CD8+ and FOXP3+ infiltration ratios were used as thresholds to dichotomise patients to either high or low infiltration rates. Prognostic variables were identified using univariate and Cox multivariate analysis. Kaplan-Meier analysis and the log-rank test were used to illustrate differences in overall survival. Results: Patients with a higher intratumoral CD3+ and CD8+ lymphocyte infiltration ratio had significantly better survival compared to those with a low tumour/stroma infiltration ratio (p=0.023 & <0.001 respectively). Conversely high intratumoral T-regulatory FOXP3+ positive lymphocyte infiltration rates were associated with a particularly poor prognosis independent of surgical stage (p<0.001). Conclusions: Microlocalization of infiltrating T-lymphocytes, in particular Treg cells, is a powerful predictor of outcome for surgically resected NSCLC and compares favourably with recently published prognostic genomic approaches. Assessment of inflammatory cell infiltrates may help determine which patients should receive adjuvant chemotherapy and, in the future, in predicting benefit from novel adjuvant vaccine/immunotherapies. No significant financial relationships to disclose.
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