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

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...

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Main Authors: Viriya Kaewkangsadan, Chandan Verma, Jennifer M. Eremin, Gerard Cowley, Mohammed Ilyas, Oleg Eremin
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Journal of Immunology Research
Online Access:http://dx.doi.org/10.1155/2016/4757405
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author Viriya Kaewkangsadan
Chandan Verma
Jennifer M. Eremin
Gerard Cowley
Mohammed Ilyas
Oleg Eremin
author_facet Viriya Kaewkangsadan
Chandan Verma
Jennifer M. Eremin
Gerard Cowley
Mohammed Ilyas
Oleg Eremin
author_sort Viriya Kaewkangsadan
collection DOAJ
description 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.
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spelling doaj-art-ee681fc08f3f433685577163a2e44cfd2025-08-20T02:21:41ZengWileyJournal of Immunology Research2314-88612314-71562016-01-01201610.1155/2016/47574054757405Crucial 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 CancerViriya Kaewkangsadan0Chandan Verma1Jennifer M. Eremin2Gerard Cowley3Mohammed Ilyas4Oleg Eremin5Division 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, UKDivision 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, UKResearch & Development Department, Lincoln Breast Unit, Lincoln County Hospital, Greetwell Road, Lincoln LN2 5QY, UKDepartment of Pathology, PathLinks, Lincoln County Hospital, Greetwell Road, Lincoln LN2 5QY, UKAcademic Department of Pathology, Faculty of Medicine and Health Sciences, University of Nottingham, A Floor, West Block, Queens Medical Centre, Derby Road, Nottingham NG7 2UH, UKDivision 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, UKThe 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.http://dx.doi.org/10.1155/2016/4757405
spellingShingle Viriya Kaewkangsadan
Chandan Verma
Jennifer M. Eremin
Gerard Cowley
Mohammed Ilyas
Oleg Eremin
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
Journal of Immunology Research
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
url http://dx.doi.org/10.1155/2016/4757405
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