Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse
IntroductionPatients with high-risk, triple negative breast cancer (TNBC) often receive neoadjuvant chemotherapy (NAC) alone or with immunotherapy. Various single-cell and spatially resolved techniques have demonstrated heterogeneity in the phenotype and distribution of macrophages and T cells in th...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-11-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1291643/full |
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| author | Mohammed Ridha Moamin Richard Allen Steven Leslie Woods Janet Elizabeth Brown Harry Nunns Anna Juncker-Jensen Claire Elizabeth Lewis |
| author_facet | Mohammed Ridha Moamin Richard Allen Steven Leslie Woods Janet Elizabeth Brown Harry Nunns Anna Juncker-Jensen Claire Elizabeth Lewis |
| author_sort | Mohammed Ridha Moamin |
| collection | DOAJ |
| description | IntroductionPatients with high-risk, triple negative breast cancer (TNBC) often receive neoadjuvant chemotherapy (NAC) alone or with immunotherapy. Various single-cell and spatially resolved techniques have demonstrated heterogeneity in the phenotype and distribution of macrophages and T cells in this form of breast cancer. Furthermore, recent studies in mice have implicated immune cells in perivascular (PV) areas of tumors in the regulation of metastasis and anti-tumor immunity. However, little is known of how the latter change during NAC in human TNBC or their impact on subsequent relapse, or the likely efficacy of immunotherapy given with or after NAC.MethodsWe have used multiplex immunofluorescence and AI-based image analysis to compare the immune landscape in untreated and NAC-treated human TNBCs. We quantified changes in the phenotype, distribution and intercellular contacts of subsets of tumor-associated macrophages (TAMs), CD4+ and CD8+ T cells, and regulatory T cells (Tregs) in PV and non-PV various areas of the stroma and tumor cell islands. These were compared in tumors from patients who had either developed metastases or were disease-free (DF) after a three-year follow up period.ResultsIn tumors from patients who remained DF after NAC, there was a marked increase in stromal CD163+ TAMs, especially those expressing the negative checkpoint regulator, T-cell immunoglobulin and mucin domain 3 (TIM-3). Whereas CD4+ T cells preferentially located to PV areas in the stroma of both untreated and NAC-treated tumors, specific subsets of TAMs and Tregs only did so only after NAC. Distinct subsets of CD4+ and CD8+ T cells formed PV clusters with CD163+ TAMs and Tregs. These were retained after NAC.DiscussionQuantification of stromal TIM-3+CD163+ TAMs in tumor residues after NAC may represent a new way of identifying patients at high risk of relapse. PV clustering of immune cells is highly likely to regulate the activation and function of T cells, and thus the efficacy of T cell-based immunotherapies administered with or after NAC. |
| first_indexed | 2024-03-09T14:20:44Z |
| format | Article |
| id | doaj.art-90b65a0739274753b52ec5008c0fc1b9 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-09T14:20:44Z |
| publishDate | 2023-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-90b65a0739274753b52ec5008c0fc1b92023-11-28T14:08:16ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-11-011410.3389/fimmu.2023.12916431291643Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapseMohammed Ridha Moamin0Richard Allen1Steven Leslie Woods2Janet Elizabeth Brown3Harry Nunns4Anna Juncker-Jensen5Claire Elizabeth Lewis6Division of Clinical Medicine, School of Medicine & Population Health, Faculty of Health, Sheffield, United KingdomDivision of Clinical Medicine, School of Medicine & Population Health, Faculty of Health, Sheffield, United KingdomDivision of Clinical Medicine, School of Medicine & Population Health, Faculty of Health, Sheffield, United KingdomDivision of Clinical Medicine, School of Medicine & Population Health, Faculty of Health, Sheffield, United KingdomNeogenomics Labs., Aliso Viejo, CA, United StatesNeogenomics Labs., Aliso Viejo, CA, United StatesDivision of Clinical Medicine, School of Medicine & Population Health, Faculty of Health, Sheffield, United KingdomIntroductionPatients with high-risk, triple negative breast cancer (TNBC) often receive neoadjuvant chemotherapy (NAC) alone or with immunotherapy. Various single-cell and spatially resolved techniques have demonstrated heterogeneity in the phenotype and distribution of macrophages and T cells in this form of breast cancer. Furthermore, recent studies in mice have implicated immune cells in perivascular (PV) areas of tumors in the regulation of metastasis and anti-tumor immunity. However, little is known of how the latter change during NAC in human TNBC or their impact on subsequent relapse, or the likely efficacy of immunotherapy given with or after NAC.MethodsWe have used multiplex immunofluorescence and AI-based image analysis to compare the immune landscape in untreated and NAC-treated human TNBCs. We quantified changes in the phenotype, distribution and intercellular contacts of subsets of tumor-associated macrophages (TAMs), CD4+ and CD8+ T cells, and regulatory T cells (Tregs) in PV and non-PV various areas of the stroma and tumor cell islands. These were compared in tumors from patients who had either developed metastases or were disease-free (DF) after a three-year follow up period.ResultsIn tumors from patients who remained DF after NAC, there was a marked increase in stromal CD163+ TAMs, especially those expressing the negative checkpoint regulator, T-cell immunoglobulin and mucin domain 3 (TIM-3). Whereas CD4+ T cells preferentially located to PV areas in the stroma of both untreated and NAC-treated tumors, specific subsets of TAMs and Tregs only did so only after NAC. Distinct subsets of CD4+ and CD8+ T cells formed PV clusters with CD163+ TAMs and Tregs. These were retained after NAC.DiscussionQuantification of stromal TIM-3+CD163+ TAMs in tumor residues after NAC may represent a new way of identifying patients at high risk of relapse. PV clustering of immune cells is highly likely to regulate the activation and function of T cells, and thus the efficacy of T cell-based immunotherapies administered with or after NAC.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1291643/fulltriple negative breast cancer (TNBC)multiplex optical bioassays, encodingbioimaging and biodectiondiagnosticsneoadjuvant chemotherapy (NAC)macrophages |
| spellingShingle | Mohammed Ridha Moamin Richard Allen Steven Leslie Woods Janet Elizabeth Brown Harry Nunns Anna Juncker-Jensen Claire Elizabeth Lewis Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse Frontiers in Immunology triple negative breast cancer (TNBC) multiplex optical bioassays, encoding bioimaging and biodection diagnostics neoadjuvant chemotherapy (NAC) macrophages |
| title | Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse |
| title_full | Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse |
| title_fullStr | Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse |
| title_full_unstemmed | Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse |
| title_short | Changes in the immune landscape of TNBC after neoadjuvant chemotherapy: correlation with relapse |
| title_sort | changes in the immune landscape of tnbc after neoadjuvant chemotherapy correlation with relapse |
| topic | triple negative breast cancer (TNBC) multiplex optical bioassays, encoding bioimaging and biodection diagnostics neoadjuvant chemotherapy (NAC) macrophages |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1291643/full |
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