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J Immunol Res. 2016;2016:4757405. Epub 2016 Sep 29.

Crucial Contributions by T Lymphocytes (Effector, Regulatory, and Checkpoint Inhibitor) and Cytokines (TH1, TH2, and TH17) to a Pathological Complete Response Induced by Neoadjuvant Chemotherapy in Women with Breast Cancer.

Author information

1
Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, Faculty of Medicine and Health Sciences, University of Nottingham, E Floor, West Block, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, UK.
2
Research & Development Department, Lincoln Breast Unit, Lincoln County Hospital, Greetwell Road, Lincoln LN2 5QY, UK.
3
Department of Pathology, PathLinks, Lincoln County Hospital, Greetwell Road, Lincoln LN2 5QY, UK.
4
Academic Department of Pathology, Faculty of Medicine and Health Sciences, University of Nottingham, A Floor, West Block, Queens Medical Centre, Derby Road, Nottingham NG7 2UH, UK.
5
Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, Faculty of Medicine and Health Sciences, University of Nottingham, E Floor, West Block, Queen's Medical Centre, Derby Rd, Nottingham NG7 2UH, UK; Research & Development Department, Lincoln Breast Unit, Lincoln County Hospital, Greetwell Road, Lincoln LN2 5QY, UK.

Abstract

The tumour microenvironment consists of malignant cells, stroma, and immune cells. Prominent tumour-infiltrating lymphocytes (TILs) in breast cancer are associated with a good prognosis and are predictors of a pathological complete response (pCR) with neoadjuvant chemotherapy (NAC). The contribution of different T effector/regulatory cells and cytokines to tumour cell death with NAC requires further characterisation and was investigated in this study. Breast tumours from 33 women with large and locally advanced breast cancers undergoing NAC were immunohistochemically (intratumoural, stromal) assessed for T cell subsets and cytokine expression using labelled antibodies, employing established semiquantitative methods. Prominent levels of TILs and CD4+, CD8+, and CTLA-4+ (stromal) T cells and CD8+ : FOXP3+ ratios were associated with a significant pCR; no association was seen with FOXP3+, CTLA-4+ (intratumoural), and PD-1+ T cells. NAC significantly reduced CD4+, FOXP3+, CTLA-4+ (stromal) (concurrently blood FOXP3+, CTLA-4+ Tregs), and PD-1+ T cells; no reduction was seen with CD8+ and CTLA-4+ (intratumoural) T cells. High post-NAC tumour levels of FOXP3+ T cells, IL-10, and IL-17 were associated with a failed pCR. Our study has characterised further the contribution of T effector/regulatory cells and cytokines to tumour cell death with NAC.

PMID:
27777963
PMCID:
PMC5061970
DOI:
10.1155/2016/4757405
[Indexed for MEDLINE]
Free PMC Article

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