Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (Th1, Th2) to immune-mediated tumour cell death induced by NAC
Abstract Background The tumour microenvironment consists of malignant cells, stroma and immune cells. In women with large and locally advanced breast cancers (LLABCs) undergoing neoadjuvant chemotherapy (NAC), tumour-infiltrating lymphocytes (TILs), various subsets (effector, regulatory) and cytokin...
Main Authors: | , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
BMC
2018-02-01
|
Series: | BMC Cancer |
Subjects: | |
Online Access: | http://link.springer.com/article/10.1186/s12885-018-4044-z |
id |
doaj-b3a29112dfc646b3804dfd0a20728dd6 |
---|---|
record_format |
Article |
spelling |
doaj-b3a29112dfc646b3804dfd0a20728dd62020-11-25T01:49:07ZengBMCBMC Cancer1471-24072018-02-0118111410.1186/s12885-018-4044-zTumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (Th1, Th2) to immune-mediated tumour cell death induced by NACViriya Kaewkangsadan0Chandan Verma1Jennifer M. Eremin2Gerard Cowley3Mohammad Ilyas4Oleg Eremin5Division of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, Faculty of Medicine and Health Sciences, University of NottinghamDivision of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, Faculty of Medicine and Health Sciences, University of NottinghamResearch & Development Department, Lincoln Breast Unit, Lincoln County HospitalDepartment of Pathology, PathLinks, Lincoln County Hospital, Greetwell RoadAcademic Department of Pathology, Faculty of Medicine and Health Sciences, University of NottinghamDivision of Gastrointestinal Surgery, Nottingham Digestive Diseases Centre, Faculty of Medicine and Health Sciences, University of NottinghamAbstract Background The tumour microenvironment consists of malignant cells, stroma and immune cells. In women with large and locally advanced breast cancers (LLABCs) undergoing neoadjuvant chemotherapy (NAC), tumour-infiltrating lymphocytes (TILs), various subsets (effector, regulatory) and cytokines in the primary tumour play a key role in the induction of tumour cell death and a pathological complete response (pCR) with NAC. Their contribution to a pCR in nodal metastases, however, is poorly studied and was investigated. Methods Axillary lymph nodes (ALNs) (24 with and 9 without metastases) from women with LLABCs undergoing NAC were immunohistochemically assessed for TILs, T effector and regulatory cell subsets, NK cells and cytokine expression using labelled antibodies, employing established semi-quantitative methods. IBM SPSS statistical package (21v) was used. Non-parametric (paired and unpaired) statistical analyses were performed. Univariate and multivariate regression analyses were carried out to establish the prediction of a pCR and Spearman’s Correlation Coefficient was used to determine the correlation of immune cell infiltrates in ALN metastatic and primary breast tumours. Results In ALN metastases high levels of TILs, CD4+ and CD8+ T and CD56+ NK cells were significantly associated with pCRs.. Significantly higher levels of Tregs (FOXP3+, CTLA-4+) and CD56+ NK cells were documented in ALN metastases than in the corresponding primary breast tumours. CD8+ T and CD56+ NK cells showed a positive correlation between metastatic and primary tumours. A high % CD8+ and low % FOXP3+ T cells and high CD8+: FOXP3+ ratio in metastatic ALNs (tumour-free para-cortex) were associated with pCRs. Metastatic ALNs expressed high IL-10, low IL-2 and IFN-ϒ. Conclusions Our study has provided new data characterising the possible contribution of T effector and regulatory cells and NK cells and T helper1 and 2 cytokines to tumour cell death associated with NAC in ALNs. Trial registration The Trial was retrospectively registered. Study Registration Number is ISRCTN00407556.http://link.springer.com/article/10.1186/s12885-018-4044-zAxillary lymph nodeBreast cancerNeoadjuvant chemotherapyTumour microenvironmentTumour-infiltrating lymphocyte subsetsCytokines |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Viriya Kaewkangsadan Chandan Verma Jennifer M. Eremin Gerard Cowley Mohammad Ilyas Oleg Eremin |
spellingShingle |
Viriya Kaewkangsadan Chandan Verma Jennifer M. Eremin Gerard Cowley Mohammad Ilyas Oleg Eremin Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (Th1, Th2) to immune-mediated tumour cell death induced by NAC BMC Cancer Axillary lymph node Breast cancer Neoadjuvant chemotherapy Tumour microenvironment Tumour-infiltrating lymphocyte subsets Cytokines |
author_facet |
Viriya Kaewkangsadan Chandan Verma Jennifer M. Eremin Gerard Cowley Mohammad Ilyas Oleg Eremin |
author_sort |
Viriya Kaewkangsadan |
title |
Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (Th1, Th2) to immune-mediated tumour cell death induced by NAC |
title_short |
Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (Th1, Th2) to immune-mediated tumour cell death induced by NAC |
title_full |
Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (Th1, Th2) to immune-mediated tumour cell death induced by NAC |
title_fullStr |
Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (Th1, Th2) to immune-mediated tumour cell death induced by NAC |
title_full_unstemmed |
Tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (NAC): the crucial contribution of immune cells (effector, regulatory) and cytokines (Th1, Th2) to immune-mediated tumour cell death induced by NAC |
title_sort |
tumour-draining axillary lymph nodes in patients with large and locally advanced breast cancers undergoing neoadjuvant chemotherapy (nac): the crucial contribution of immune cells (effector, regulatory) and cytokines (th1, th2) to immune-mediated tumour cell death induced by nac |
publisher |
BMC |
series |
BMC Cancer |
issn |
1471-2407 |
publishDate |
2018-02-01 |
description |
Abstract Background The tumour microenvironment consists of malignant cells, stroma and immune cells. In women with large and locally advanced breast cancers (LLABCs) undergoing neoadjuvant chemotherapy (NAC), tumour-infiltrating lymphocytes (TILs), various subsets (effector, regulatory) and cytokines in the primary tumour play a key role in the induction of tumour cell death and a pathological complete response (pCR) with NAC. Their contribution to a pCR in nodal metastases, however, is poorly studied and was investigated. Methods Axillary lymph nodes (ALNs) (24 with and 9 without metastases) from women with LLABCs undergoing NAC were immunohistochemically assessed for TILs, T effector and regulatory cell subsets, NK cells and cytokine expression using labelled antibodies, employing established semi-quantitative methods. IBM SPSS statistical package (21v) was used. Non-parametric (paired and unpaired) statistical analyses were performed. Univariate and multivariate regression analyses were carried out to establish the prediction of a pCR and Spearman’s Correlation Coefficient was used to determine the correlation of immune cell infiltrates in ALN metastatic and primary breast tumours. Results In ALN metastases high levels of TILs, CD4+ and CD8+ T and CD56+ NK cells were significantly associated with pCRs.. Significantly higher levels of Tregs (FOXP3+, CTLA-4+) and CD56+ NK cells were documented in ALN metastases than in the corresponding primary breast tumours. CD8+ T and CD56+ NK cells showed a positive correlation between metastatic and primary tumours. A high % CD8+ and low % FOXP3+ T cells and high CD8+: FOXP3+ ratio in metastatic ALNs (tumour-free para-cortex) were associated with pCRs. Metastatic ALNs expressed high IL-10, low IL-2 and IFN-ϒ. Conclusions Our study has provided new data characterising the possible contribution of T effector and regulatory cells and NK cells and T helper1 and 2 cytokines to tumour cell death associated with NAC in ALNs. Trial registration The Trial was retrospectively registered. Study Registration Number is ISRCTN00407556. |
topic |
Axillary lymph node Breast cancer Neoadjuvant chemotherapy Tumour microenvironment Tumour-infiltrating lymphocyte subsets Cytokines |
url |
http://link.springer.com/article/10.1186/s12885-018-4044-z |
work_keys_str_mv |
AT viriyakaewkangsadan tumourdrainingaxillarylymphnodesinpatientswithlargeandlocallyadvancedbreastcancersundergoingneoadjuvantchemotherapynacthecrucialcontributionofimmunecellseffectorregulatoryandcytokinesth1th2toimmunemediatedtumourcelldeathinducedbynac AT chandanverma tumourdrainingaxillarylymphnodesinpatientswithlargeandlocallyadvancedbreastcancersundergoingneoadjuvantchemotherapynacthecrucialcontributionofimmunecellseffectorregulatoryandcytokinesth1th2toimmunemediatedtumourcelldeathinducedbynac AT jennifermeremin tumourdrainingaxillarylymphnodesinpatientswithlargeandlocallyadvancedbreastcancersundergoingneoadjuvantchemotherapynacthecrucialcontributionofimmunecellseffectorregulatoryandcytokinesth1th2toimmunemediatedtumourcelldeathinducedbynac AT gerardcowley tumourdrainingaxillarylymphnodesinpatientswithlargeandlocallyadvancedbreastcancersundergoingneoadjuvantchemotherapynacthecrucialcontributionofimmunecellseffectorregulatoryandcytokinesth1th2toimmunemediatedtumourcelldeathinducedbynac AT mohammadilyas tumourdrainingaxillarylymphnodesinpatientswithlargeandlocallyadvancedbreastcancersundergoingneoadjuvantchemotherapynacthecrucialcontributionofimmunecellseffectorregulatoryandcytokinesth1th2toimmunemediatedtumourcelldeathinducedbynac AT olegeremin tumourdrainingaxillarylymphnodesinpatientswithlargeandlocallyadvancedbreastcancersundergoingneoadjuvantchemotherapynacthecrucialcontributionofimmunecellseffectorregulatoryandcytokinesth1th2toimmunemediatedtumourcelldeathinducedbynac |
_version_ |
1725008815305261056 |