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
Background and Aim: 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 cytok...
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| Format: | Article |
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BioMed Central
2016
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| Online Access: | https://eprints.nottingham.ac.uk/33127/ |
| _version_ | 1848794563520495616 |
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| author | Kaewkangsadan, Viriya Verma, Chandan Eremin, Jennifer M. Cowley, Gerard P. |
| author_facet | Kaewkangsadan, Viriya Verma, Chandan Eremin, Jennifer M. Cowley, Gerard P. |
| author_sort | Kaewkangsadan, Viriya |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background and Aim:
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. The contribution of the cellular and humoral responses to a pCR in nodal metastases, however, is poorly studied and was investigated.
Patients and Methods:
Axillary lymph nodes (ALNs) (24 with and 9 without metastases) from women with LLABCs undergoing NAC were immunohistochemically assessed for TILs, T cell subsets, NK cells and cytokine expression using labelled antibodies, employing established semi-quantitative methods.
Results:
In ALN metastases high levels of TILs, CD4+ and CD8+ T and CD56+ NK cells were significantly associated with pCRs. High levels of TILs and CD56+ NK cells in ALN metastases were independent predictors (univariate analysis) of a pCR with NAC. 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 paracortex) were associated with pCRs. Metastatic ALNs expressed high IL-10, low IL-2 and IFN-ϒ.
Conclusion:
Our study has provided new data characterising the possible contribution of T effector/regulatory and NK cells and cytokines to tumour cell death with NAC. |
| first_indexed | 2025-11-14T19:18:11Z |
| format | Article |
| id | nottingham-33127 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:18:11Z |
| publishDate | 2016 |
| publisher | BioMed Central |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-331272020-05-04T20:02:43Z https://eprints.nottingham.ac.uk/33127/ 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 Kaewkangsadan, Viriya Verma, Chandan Eremin, Jennifer M. Cowley, Gerard P. Background and Aim: 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. The contribution of the cellular and humoral responses to a pCR in nodal metastases, however, is poorly studied and was investigated. Patients and Methods: Axillary lymph nodes (ALNs) (24 with and 9 without metastases) from women with LLABCs undergoing NAC were immunohistochemically assessed for TILs, T cell subsets, NK cells and cytokine expression using labelled antibodies, employing established semi-quantitative methods. Results: In ALN metastases high levels of TILs, CD4+ and CD8+ T and CD56+ NK cells were significantly associated with pCRs. High levels of TILs and CD56+ NK cells in ALN metastases were independent predictors (univariate analysis) of a pCR with NAC. 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 paracortex) were associated with pCRs. Metastatic ALNs expressed high IL-10, low IL-2 and IFN-ϒ. Conclusion: Our study has provided new data characterising the possible contribution of T effector/regulatory and NK cells and cytokines to tumour cell death with NAC. BioMed Central 2016-05 Article NonPeerReviewed Kaewkangsadan, Viriya, Verma, Chandan, Eremin, Jennifer M. and Cowley, Gerard P. (2016) 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. Breast Cancer Research . ISSN 1465-542X (Submitted) Axillary lymph node; breast cancer neoadjuvant chemotherapy tumour microenvironment tumour-infiltrating lymphocyte subsets cytokines. |
| spellingShingle | Axillary lymph node; breast cancer neoadjuvant chemotherapy tumour microenvironment tumour-infiltrating lymphocyte subsets cytokines. Kaewkangsadan, Viriya Verma, Chandan Eremin, Jennifer M. Cowley, Gerard P. 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 | 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_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_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 |
| topic | Axillary lymph node; breast cancer neoadjuvant chemotherapy tumour microenvironment tumour-infiltrating lymphocyte subsets cytokines. |
| url | https://eprints.nottingham.ac.uk/33127/ |