Griguolo, G.Serna, G.Pascual, T.Fasani, RobertaGuardia, X.Chic, N.Pare, L.Pernas, S.Munoz, M.Oliveira, M.Vidal, M.Llombart-Cussac, A.Cortés, JavierGalvan, P.Bermejo, BegoñaMartinez, N.Lopez, R.Morales, S.Garau, IManso, L.Alarcón Company, JesúsVillagrasa, P.Prat, A.Nuciforo, Paolo2023-09-262023-09-262021-03-19Griguolo G, Serna G, Pascual T, Fasani R, Guardia X, Chic N, et al. Immune microenvironment characterisation and dynamics during anti-HER2-based neoadjuvant treatment in HER2-positive breast cancer. NPJ Precis Oncol. 2021 Mar 19;5(1):23.https://hdl.handle.net/20.500.13003/19632Despite 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.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/research article10.1038/s41698-021-00163-62397-768X33742063L20108481802-s2.0-85112019288631563100004open access