Abstract | 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 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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Authors | Kei Suzuki, Kyuichi Kadota, Camelia S Sima, Jun-ichi Nitadori, Valerie W Rusch, William D Travis, Michel Sadelain, Prasad S Adusumilli |
Journal | Journal 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 |
PMID | 23269987
(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.)
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Chemical References |
- Biomarkers, Tumor
- CD3 Complex
- FOXP3 protein, human
- Forkhead Transcription Factors
- IL12RB2 protein, human
- Receptors, Interleukin-12
- Receptors, Interleukin-7
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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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