Griguolo, GaiaSerna, G.Pascual, TomásFasani, R.Guardia, X.Chic Ruché, NúriaParé, LaiaPernas, SòniaMuñoz Mateu, MontserratOliveira, MafaldaVidal, M.Llombart Cussac, AntonioCortés, JavierGalván, PatriciaBermejo de las Heras, BegoñaMartínez, N.López, R.Morales, SerafínGarau, IsabelManso, LuisAlarcón, JesúsMartínez, E.Villagrasa, PatriciaPrat Aparicio, AleixNuciforo, Paolo2021-04-082021-04-082021-03-19https://hdl.handle.net/2445/176098Despite 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.12 p.application/pdfengcc by (c) Griguolo, G. et al., 2021http://creativecommons.org/licenses/by/3.0/es/Càncer de mamaPronòstic mèdicExpressió gènicaBreast cancerPrognosisGene expressioninfo:eu-repo/semantics/article2021-04-08info:eu-repo/semantics/openAccess33742063