Tumour-infiltrating FOXP3+ lymphocytes are associated with cytotoxic immune responses and good clinical outcome in oestrogen receptor-negative breast cancer

• Published in: British journal of cancer Vol. 108; no. 1; pp. 155 - 162
• Main Authors: West, N R, Kost, S E, Martin, S D, Milne, K, deLeeuw, R J, Nelson, B H, Watson, P H
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.01.2013; Nature Publishing Group
• Subjects: 631/250/1619/554/1898/1271; 692/699/67/1347; 692/700/1750; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Breast Neoplasms - immunology; Breast Neoplasms - metabolism; Cancer Research; Clinical outcomes; Drug Resistance; Epidemiology; Female; Forkhead Transcription Factors - metabolism; Gynecology. Andrology. Obstetrics; Humans; Lymphocytes, Tumor-Infiltrating - immunology; Lymphocytes, Tumor-Infiltrating - metabolism; Mammary gland diseases; Medical sciences; Middle Aged; Molecular Diagnostics; Molecular Medicine; Oncology; Prognosis; T-Lymphocytes, Cytotoxic - immunology; Tissue Array Analysis; Tumors; oestrogen receptor; FOXP3; prognosis; Treg; tumour immunity breast cancer; Estrogen receptor; Breast disease; Prognosis; Immune response; Breast tumor; Cytotoxicity; Breast cancer; Tumor infiltrating lymphocyte; Malignant tumor; Immunity; Mammary gland diseases; Cancerology; Transcription factor FOXP3; Cancer; Hormonal receptor
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2012.524

Background: Regulatory T cells (Tregs) are commonly identified by expression of the transcription factor FOXP3 and are conventionally thought to promote cancer progression by suppressing anti-tumour immune responses. We examined the relationship between FOXP3 + tumour-infiltrating lymphocytes (TIL) and prognosis in oestrogen receptor (ER)-negative breast cancer, a tumour subtype with poor clinical outcome in which TIL are abundant. Methods: FOXP3 + and CD8 + TIL were assessed by immunohistochemistry in a cohort of 175 ER– breast tumours. Results were confirmed in an independent data set of 78 ER– breast tumours with publically available gene expression data. Results: High FOXP3 + TIL levels were strongly associated with prolonged recurrence-free survival (HR=0.461, P =0.0002), particularly among basal-like tumours (HR=0.280, P =0.0001), for which FOXP3 status was independent of standard prognostic factors. Over 75% of FOXP3 + TIL in triple negative breast tumours displayed a conventional CD4 + CD25 + Treg phenotype. Importantly, FOXP3 + TIL were positively correlated with CD8 + (cytotoxic) T cells ( r s =0.76, P <0.0001), and were prognostically insignificant in tumours with low levels of CD8 + TIL. These observations were confirmed in an independent cohort. Conclusion: In contrast with current dogma, we show for the first time that FOXP3 + TIL are associated with robust anti-tumour immunity and favourable prognosis in ER– breast cancer.