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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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/c2515a92ad4548f9831b897df5db6552
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spelling	oai:doaj.org-article:c2515a92ad4548f9831b897df5db65522021-12-02T11:39:42ZImmune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer10.1038/s41698-021-00163-62397-768Xhttps://doaj.org/article/c2515a92ad4548f9831b897df5db65522021-03-01T00:00:00Zhttps://doi.org/10.1038/s41698-021-00163-6https://doaj.org/toc/2397-768XAbstract 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.G. GriguoloG. SernaT. PascualR. FasaniX. GuardiaN. ChicL. ParéS. PernasM. MuñozM. OliveiraM. VidalA. Llombart-CussacJ. CortésP. GalvánB. BermejoN. MartínezR. LópezS. MoralesI. GarauL. MansoJ. AlarcónE. MartínezP. VillagrasaA. PratP. NuciforoNature PortfolioarticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENnpj Precision Oncology, Vol 5, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 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
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.
format	article
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
title	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_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_sort	immune microenvironment characterisation and dynamics during anti-her2-based neoadjuvant treatment in her2-positive breast cancer
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c2515a92ad4548f9831b897df5db6552
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Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer

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