Tumor infiltrating Foxp3+ regulatory T‐cells are associated with recurrence in pathologic stage I NSCLC patients

• Published in: Cancer Vol. 107; no. 12; pp. 2866 - 2872
• Main Authors: Petersen, Rebecca P., Campa, Michael J., Sperlazza, Justin, Conlon, Debbi, Joshi, Mary‐Beth, Harpole, David H., Patz, Edward F.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.12.2006; Wiley-Liss
• Subjects: Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - pathology; CD3 Complex - analysis; Forkhead Transcription Factors - analysis; Humans; immunohistochemistry; lung cancer; Lung Neoplasms - diagnosis; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lymphocytes, Tumor-Infiltrating - chemistry; Lymphocytes, Tumor-Infiltrating - immunology; Medical sciences; Neoplasm Recurrence, Local - diagnosis; Neoplasm Recurrence, Local - immunology; Neoplasm Recurrence, Local - pathology; Neoplasm Staging; Pneumology; Prognosis; regulatory T cells; T-Lymphocytes, Regulatory - chemistry; T-Lymphocytes, Regulatory - immunology; Tumors; Tumors of the respiratory system and mediastinum; Human; Immunohistochemistry; Lung disease; Relapse; Prognosis; Respiratory disease; Lung cancer; Early stage; Malignant tumor; Infiltrating tumor; regulatory T cells; Anatomic pathology; Cancerology; T-Lymphocyte; Bronchus disease; Regulatory cell; Transcription factor FOXP3; Tumor cell
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.22282

BACKGROUND. Early stage lung cancer has a variable prognosis, and there are currently no markers that predict which patients will recur. This study examined the relation between tumor‐regulatory T (Treg) cells and total tumor‐infiltrating T‐cell lymphocytes (TIL) to determine whether they correlated with recurrence. METHODS. The authors reviewed all patients in our tissue databank from 1996 to 2001 and identified 64 consecutive pathologic stage I non‐small cell lung cancer (NSCLC) patients who had surgical resection and at least a 2.5 years disease‐free follow‐up or documented recurrence within 2 years. Immunohistochemical analyses were performed on paraffin‐embedded lung cancer tissue and the relation between Treg cells, TIL, and disease‐specific survival was determined. A risk index was devised deductively for various possible combinations of Treg cells and TIL. RESULTS. Treg cells and TIL were detected in 33 of 64 (51%) and 53 of 64 (83%) patients, respectively. When data were analyzed by using a Treg/TIL Combination Risk Index, patients with high‐risk and intermediate‐risk indices had hazard ratios of 8.2 (P = .007) and 3.3 (P = .109), respectively. CONCLUSIONS. Patients with stage I NSCLC who have a higher proportion of tumor Treg cells relative to TIL had a significantly higher risk of recurrence. These data may be useful, particularly if combined with a panel of tumor markers, to suggest at the time of diagnosis which patients with seemingly early‐stage NSCLC will relapse. Cancer 2006. © 2006 American Cancer Society. Regulatory T‐cells represent a subset of total tumor‐infiltrating T lymphocytes and are present in various amounts in pathologic stage I NSCLC tumors. Early stage lung cancers that have a greater proportion of regulatory T‐cells relative to total tumor‐infiltrating T lymphocytes have a significantly higher risk of recurrence.