Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor ß2 (IL-12Rß2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence.

Journal of Clinical Oncology

PubMedID: 23269987

Suzuki K, Kadota K, Sima CS, Nitadori J, Rusch VW, Travis WD, Sadelain M, Adusumilli PS. Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor ß2 (IL-12Rß2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence. J Clin Oncol. 2013;31(4):490-8.
PURPOSE
Mounting 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).

RESULTS
Although 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 ß2 (IL-12Rß2) 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.