Tumour islet Foxp3+ T-cell infiltration predicts poor outcome in nonsmall cell lung cancer

• Published in: The European respiratory journal Vol. 46; no. 6; pp. 1762 - 1772
• Main Authors: O'Callaghan, Dermot S, Rexhepaj, Elton, Gately, Kathy, Coate, Linda, Delaney, David, O'Donnell, Dearbhaile M, Kay, Elaine, O'Connell, Finbarr, Gallagher, William M, O'Byrne, Kenneth J
• Format: Journal Article
• Language: English
• Published: England 01-12-2015
• Subjects: Adenocarcinoma - genetics; Adenocarcinoma - immunology; Adenocarcinoma - pathology; Adenocarcinoma - surgery; Adult; Aged; Aged, 80 and over; Algorithms; Carcinoma, Large Cell - genetics; Carcinoma, Large Cell - immunology; Carcinoma, Large Cell - pathology; Carcinoma, Large Cell - surgery; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - immunology; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - surgery; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; Cohort Studies; Female; Forkhead Transcription Factors - metabolism; Humans; Image Processing, Computer-Assisted; Immunohistochemistry; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Lymphocyte Count; Male; Middle Aged; Multivariate Analysis; Neoplasm Staging; Neoplasm, Residual; Pneumonectomy; Prognosis; Proportional Hazards Models; Proto-Oncogene Proteins p21(ras) - genetics; Receptor, Epidermal Growth Factor - genetics; Retrospective Studies; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Tumor Burden
• ISSN: 0903-1936; 1399-3003
• DOI: 10.1183/13993003.00176-2014

The impact of host immunity on outcome in nonsmall cell lung cancer (NSCLC) is controversial. We examined the relationship between lymphoid infiltration patterns in NSCLC and prognosis.Tumour- and stroma-infiltrating CD3(+), CD8(+) and forkhead box P3 (Foxp3)(+) T-lymphocytes were identified using immunohistochemistry and a novel image analysis algorithm to assess total, cytotoxic and regulatory T-lymphocyte counts, respectively, in 196 NSCLC cases. The median cell count was selected as a cut-point to define patient subgroups and the ratio of the corresponding tumour islet:stroma (TI/S) counts was determined.There was a positive association between overall survival and increased CD8(+) TI/S ratio (hazard ratio (HR) for death 0.44, p<0.001) but an inverse relationship between Foxp3(+) TI/S ratio and overall survival (HR 4.86, p<0.001). Patients with high CD8(+) islet (HR 0.48, p<0.001) and Foxp3(+) stromal (HR 0.23, p<0.001) counts had better survival, whereas high CD3(+) and CD8(+) stromal counts and high Foxp3(+) islet infiltration conferred a worse survival (HR 1.55, 2.19 and 3.14, respectively). By multivariate analysis, a high CD8(+) TI/S ratio conferred an improved survival (HR 0.48, p=0.002) but a high Foxp3(+) TI/S ratio was associated with worse survival (HR 3.91, p<0.001).Microlocalisation of infiltrating T-lymphocytes is a powerful predictor of outcome in resected NSCLC.