Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer
Abstract Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-i...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2021-03-01
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| Series: | npj Precision Oncology |
| Online Access: | https://doi.org/10.1038/s41698-021-00163-6 |
| _version_ | 1797421420010012672 |
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| author | G. Griguolo G. Serna T. Pascual R. Fasani X. Guardia N. Chic L. Paré S. Pernas M. Muñoz M. Oliveira M. Vidal A. Llombart-Cussac J. Cortés P. Galván B. Bermejo N. Martínez R. López S. Morales I. Garau L. Manso J. Alarcón E. Martínez P. Villagrasa A. Prat P. Nuciforo |
| author_facet | G. Griguolo G. Serna T. Pascual R. Fasani X. Guardia N. Chic L. Paré S. Pernas M. Muñoz M. Oliveira M. Vidal A. Llombart-Cussac J. Cortés P. Galván B. Bermejo N. Martínez R. López S. Morales I. Garau L. Manso J. Alarcón E. Martínez P. Villagrasa A. Prat P. Nuciforo |
| author_sort | G. Griguolo |
| collection | DOAJ |
| description | Abstract Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC. |
| first_indexed | 2024-03-09T07:15:54Z |
| format | Article |
| id | doaj.art-c2515a92ad4548f9831b897df5db6552 |
| institution | Directory Open Access Journal |
| issn | 2397-768X |
| language | English |
| last_indexed | 2024-03-09T07:15:54Z |
| publishDate | 2021-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Precision Oncology |
| spelling | doaj.art-c2515a92ad4548f9831b897df5db65522023-12-03T08:34:44ZengNature Portfolionpj Precision Oncology2397-768X2021-03-015111210.1038/s41698-021-00163-6Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancerG. Griguolo0G. Serna1T. Pascual2R. Fasani3X. Guardia4N. Chic5L. Paré6S. Pernas7M. Muñoz8M. Oliveira9M. Vidal10A. Llombart-Cussac11J. Cortés12P. Galván13B. Bermejo14N. Martínez15R. López16S. Morales17I. Garau18L. Manso19J. Alarcón20E. Martínez21P. Villagrasa22A. Prat23P. Nuciforo24Department of Surgery, Oncology and Gastroenterology, University of PadovaMolecular oncology group, Vall d´Hebron Institute of OncologyTranslational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS)Molecular oncology group, Vall d´Hebron Institute of OncologyMolecular oncology group, Vall d´Hebron Institute of OncologyTranslational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS)SOLTI Breast Cancer Research GroupInstitut Catala d’Oncologia-H.U.Bellvitge-IDIBELL, HospitaletDepartment of Medical Oncology, Hospital Clínic de BarcelonaMedical Oncology Department, Vall d’Hebrón University HospitalDepartment of Medical Oncology, Hospital Clínic de BarcelonaHospital Universitario Arnau de Vilanova de ValenciaIOB Institute of Oncology, Quironsalud GroupTranslational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS)Hospital Clínico Universitario de Valencia/INCLIVA/CIBERONCHospital Universitario Ramón y CajalHospital Clínico Universitario de Santiago, IDIS, CIBERONCHospital Universitario Arnau de Vilanova de LleidaHospital Son LlàtzerHospital Universitario 12 de OctubreHospital Universitario Son EspasesConsorcio Hospitalario Provincial de CastellónSOLTI Breast Cancer Research GroupTranslational Genomics and Targeted Therapeutics in Solid Tumors, August Pi i Sunyer Biomedical Research Institute (IDIBAPS)Molecular oncology group, Vall d´Hebron Institute of OncologyAbstract Despite their recognised role in HER2-positive (HER2+) breast cancer (BC), the composition, localisation and functional orientation of immune cells within tumour microenvironment, as well as its dynamics during anti-HER2 treatment, is largely unknown. We here investigate changes in tumour-immune contexture, as assessed by stromal tumour-infiltrating lymphocytes (sTILs) and by multiplexed spatial cellular phenotyping, during treatment with lapatinib-trastuzumab in HER2+ BC patients (PAMELA trial). Moreover, we evaluate the relationship of tumour-immune contexture with hormone receptor status, intrinsic subtype and immune-related gene expression. sTIL levels increase after 2 weeks of HER2 blockade in HR-negative disease and HER2-enriched subtype. This is linked to a concomitant increase in cell density of all four immune subpopulations (CD3+, CD4+, CD8+, Foxp3+). Moreover, immune contexture analysis showed that immune cells spatially interacting with tumour cells have the strongest association with response to anti-HER2 treatment. Subsequently, sTILs consistently decrease at the surgery in patients achieving pathologic complete response, whereas most residual tumours at surgery remain inflamed, possibly reflecting a progressive loss of function of T cells. Understanding the features of the resulting tumour immunosuppressive microenvironment has crucial implications for the design of new strategies to de-escalate or escalate systemic therapy in early-stage HER2+ BC.https://doi.org/10.1038/s41698-021-00163-6 |
| spellingShingle | G. Griguolo G. Serna T. Pascual R. Fasani X. Guardia N. Chic L. Paré S. Pernas M. Muñoz M. Oliveira M. Vidal A. Llombart-Cussac J. Cortés P. Galván B. Bermejo N. Martínez R. López S. Morales I. Garau L. Manso J. Alarcón E. Martínez P. Villagrasa A. Prat P. Nuciforo Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer npj Precision Oncology |
| title | Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer |
| title_full | Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer |
| title_fullStr | Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer |
| title_full_unstemmed | Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer |
| title_short | Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer |
| title_sort | immune microenvironment characterisation and dynamics during anti her2 based neoadjuvant treatment in her2 positive breast cancer |
| url | https://doi.org/10.1038/s41698-021-00163-6 |
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