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Title: Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer
Author: Griguolo, Gaia
Serna, G.
Pascual, Tomás
Fasani, R.
Guardia, X.
Chic, Núria
Paré, Laia
Pernas, Sònia
Muñoz Mateu, Montserrat
Oliveira, Mafalda
Vidal, M.
Llombart Cussac, Antonio
Cortés, Javier
Galván, Patricia
Bermejo de las Heras, Begoña
Martínez, N.
López, R.
Morales, Serafín
Garau, Isabel
Manso, Luis
Alarcón, Jesús
Martínez, E.
Villagrasa, Patricia
Prat Aparicio, Aleix
Nuciforo, Paolo
Keywords: Càncer de mama
Pronòstic mèdic
Expressió gènica
Breast cancer
Gene expression
Issue Date: 19-Mar-2021
Publisher: Springer Science and Business Media LLC
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.
Note: Reproducció del document publicat a:
It is part of: npj Precision Oncology, 2021, vol. 5, num.23
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)

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