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Clinical impact of immune microenvironment in stage I lung adenocarcinoma: tumor interleukin-12 receptor β2 (IL-12Rβ2), IL-7R, and stromal FoxP3/CD3 ratio are independent predictors of recurrence.

AbstractPURPOSE:
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 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.
AuthorsKei Suzuki, Kyuichi Kadota, Camelia S Sima, Jun-ichi Nitadori, Valerie W Rusch, William D Travis, Michel Sadelain, Prasad S Adusumilli
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 31 Issue 4 Pg. 490-8 (Feb 01 2013) ISSN: 1527-7755 [Electronic] United States
PMID23269987 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Biomarkers, Tumor
  • CD3 Complex
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • IL12RB2 protein, human
  • Receptors, Interleukin-12
  • Receptors, Interleukin-7
Topics
  • Adenocarcinoma (immunology, mortality, pathology, surgery)
  • Adenocarcinoma of Lung
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor (analysis)
  • CD3 Complex (analysis)
  • Female
  • Forkhead Transcription Factors (analysis)
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Lung Neoplasms (immunology, mortality, pathology, surgery)
  • Lymphatic Metastasis
  • Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local (immunology)
  • Neoplasm Staging
  • Predictive Value of Tests
  • Receptors, Interleukin-12 (analysis)
  • Receptors, Interleukin-7 (analysis)
  • Risk Assessment
  • Risk Factors
  • Tissue Array Analysis

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