Dataset Information

Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit.

ABSTRACT:

Background

Optimising the selection of HER2-targeted regimens by identifying subsets of HER2-positive breast cancer (BC) patients who need more or less therapy remains challenging. We analysed BC samples before and after treatment with 1 cycle of trastuzumab according to the response to trastuzumab.

Methods

Gene expression profiles of pre- and post-treatment tumour samples from 17 HER2-positive BC patients were analysed on the Illumina platform. Tumour-associated immune pathways and blood counts were analysed with regard to the response to trastuzumab. HER2-positive murine models with differential responses to trastuzumab were used to reproduce and better characterise these data.

Results

Patients who responded to single-agent trastuzumab had basal tumour biopsies that were enriched in immune pathways, particularly the MHC-II metagene. One cycle of trastuzumab modulated the expression levels of MHC-II genes, which increased in patients who had a complete response on treatment with trastuzumab and chemotherapy. Trastuzumab increased the MHC-II-positive cell population, primarily macrophages, only in the tumour microenvironment of responsive mice. In patients who benefited from complete trastuzumab therapy and in mice that harboured responsive tumours circulating neutrophil levels declined, but this cell subset rose in nonresponsive tumours.

Conclusions

Short treatment with trastuzumab induces local and systemic immunomodulation that is associated with clinical outcomes.

SUBMITTER: Triulzi T

PROVIDER: S-EPMC6288086 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit.

Triulzi Tiziana T Regondi Viola V De Cecco Loris L Cappelletti Maria Rosa MR Di Modica Martina M Paolini Biagio B Lollini Pier Luigi PL Di Cosimo Serena S Sfondrini Lucia L Generali Daniele D Tagliabue Elda E

British journal of cancer 20181127 12

<h4>Background</h4>Optimising the selection of HER2-targeted regimens by identifying subsets of HER2-positive breast cancer (BC) patients who need more or less therapy remains challenging. We analysed BC samples before and after treatment with 1 cycle of trastuzumab according to the response to trastuzumab.<h4>Methods</h4>Gene expression profiles of pre- and post-treatment tumour samples from 17 HER2-positive BC patients were analysed on the Illumina platform. Tumour-associated immune pathways a ...[more]

PMID: 30478407

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Dataset Information

Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit.

Background

Methods

Results

Conclusions

Publications

Early immune modulation by single-agent trastuzumab as a marker of trastuzumab benefit.

Similar Datasets

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