Clinical Impact of Immune Microenvironment in Stage I Lung Adenocarcinoma: Tumor Interleukin-12 Receptor 2 (IL-12R 2), IL-7R, and Stromal FoxP3/CD3 Ratio Are Independent Predictors of Recurrence

and Michel Sadelain and Prasad S. Adusumilli, Center for Cell Engineering, Memorial Sloan-Kettering Cancer Center, New York, NY.
Journal of Clinical Oncology (Impact Factor: 18.43). 12/2012; 31(4). DOI: 10.1200/JCO.2012.45.2052
Source: PubMed


PURPOSEMounting evidence suggests that tumor-infiltrating immune cells have prognostic value for patients with solid organ malignancies. Our aim was to investigate the prognostic significance of the immune microenvironment in patients with stage I lung adenocarcinoma (ADC). PATIENTS AND METHODS
Using tissue microarray and immunohistochemistry, we investigated eight types of tumor-infiltrating immune cells in the tumor nest and tumor-associated stroma as well as tumor expression of five cytokines in a uniform cohort of 956 patients with stage I lung ADC (478 each in training and validation cohorts).ResultsAlthough a high density of stromal forkhead box P3 (FoxP3) -positive cells was associated with shorter recurrence-free probability (RFP; P = .043), the relative proportion of stromal FoxP3 to CD3 was a stronger predictor of recurrence (5-year RFP, 85% for high v 77% for low ratio; P = .004). High expression of tumor interleukin-12 receptor β2 (IL-12Rβ2) was associated with better outcome (5-year RFP, 90% for high v 80% for low expression; P = .026), whereas high expression of tumor IL-7R was associated with worse outcome (5-year RFP, 76% for high v 86% for low expression; P = .001). In multivariate analysis, these immune markers were independently associated with recurrence. Although IL-7R remained significant for poor overall survival, all the markers remained prognostic for recurrence in patients with stages IA and IB disease as well as for patients with tumors ≤ 2 cm. CONCLUSION
Our investigation confirms the biologic and prognostic significance of the tumor immune microenvironment for patients with stage I lung ADC and provides support for its use to stratify clinical outcome and immunotherapeutic interventions.

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