T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers

Rody, Achim; Holtrich, Uwe; Pusztai, L.; Liedtke, Cornelia; Gaetje, R.; Ruckhaeberle, Eugen; Solbach, Christine; Hanker, Lars; Ahr, A.; Metzler, Dirk; Engels, Knut; Karn, Thomas; Kaufmann, M.

doi:10.1186/bcr2234

Cited by 403 publications

(402 citation statements)

References 55 publications

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“…18,29,30 Therefore, although a number of gene expression signatures have been published revealing high levels of molecular heterogeneity in immune infiltration, [31][32][33][34] pathological assessment remains critical for discerning tumor spatial heterogeneity. Lymphocytes can be identified based on their typical morphology of small, round and homogeneously basophilic nuclei which differentiates them from other leukocytes, such as neutrophils with more elongated and segmented nuclei.…”

Section: Immune Cellsmentioning

confidence: 99%

Mapping spatial heterogeneity in the tumor microenvironment: a new era for digital pathology

Heindl

Nawaz

Yuan

2015

Laboratory Investigation

185

148

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The emergent field of digital pathology employing automated image analysis techniques is to revolutionize traditional pathology at the center of clinical diagnostics. Histological images provide important tumor features unavailable in molecular profiling or omics data-the spatial context of tumor and stromal cells at single-cell resolution. Methods to map the spatial and morphological patterns of cancer and normal cells can contribute to a more comprehensive understanding of the highly heterogeneous tumor microenvironment. This review focuses on methods that help expand our knowledge of intra-tumoral spatial heterogeneity of the tumor microenvironment and their potential synergies with molecular profiling technologies.

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Section: Immune Cellsmentioning

confidence: 99%

Mapping spatial heterogeneity in the tumor microenvironment: a new era for digital pathology

Heindl

Nawaz

Yuan

2015

Laboratory Investigation

185

148

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“…It is an antibody-drug conjugate cancer-killing agent combined with targeted antibody trastuzumab (Herceptin). A study has demonstrated that in 25% of breast cancer females who were victims' of HER2 overexpression, T-DM1 frequently overcomed the breast tumors and allowed the patients to go into remission (Rody et al, 2009;Yu-Ting et al, 2011).…”

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Breast Cancer: Major Risk Factors and Recent Developments in Treatment

Majeed

Aslam²,

Javed³

et al. 2014

Asian Pacific Journal of Cancer Prevention

164

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Breast cancer is the most common in women worldwide, with some 5-10% of all cases due to inherited mutations of BRCA1 and BRCA2 genes. Obesity, hormone therapy and use of alcohol are possible causes and over-expression of leptin in adipose tissue may also play a role. Normally surgery, radiation therapy and chemotherapy allow a good prognosis where screening measures are in place. New hope in treatment measures include adjuvant therapy, neoadjuvant therapy, and introduction of mono-clonal antibodies and enzyme inhibitors.

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“…These studies describe clusters of coordinately expressed genes that quantify the relative abundance and functions of tumor infiltrating immune cell populations and associate with patient outcomes. 14–18 In a recent report, we described three such prognostic immune signatures in breast tumors, each comprised of tens of genes with immune-specialized functions and expression patterns unique to immune cell populations. 19–21 These signatures, or metagenes, reflect the intratumoral presence of different immune cell lineages: T cells/NK cells (T/NK metagene) comprised of genes with functional roles in cytotoxic T-cell and NK-cell activation, B cells/plasma cells (B/P metagene) marked by IgG antibody isotype-related genes, and Myeloid/Dendritic cells (M/D metagene) delineated by genes encoding myeloid-specific and MHC-class II antigen-presenting molecules.…”

Section: Introductionmentioning

confidence: 99%

Tumor mutational burden is a determinant of immune-mediated survival in breast cancer

et al. 2018

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Mounting evidence supports a role for the immune system in breast cancer outcomes. The ability to distinguish highly immunogenic tumors susceptible to anti-tumor immunity from weakly immunogenic or inherently immune-resistant tumors would guide development of therapeutic strategies in breast cancer. Genomic, transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) breast cancer cohorts were used to examine statistical associations between tumor mutational burden (TMB) and the survival of patients whose tumors were assigned to previously-described prognostic immune subclasses reflecting favorable, weak or poor immune-infiltrate dispositions (FID, WID or PID, respectively). Tumor immune subclasses were associated with survival in patients with high TMB (TMB-Hi, P < 0.001) but not in those with low TMB (TMB-Lo, P = 0.44). This statistical relationship was confirmed in the METABRIC cohort (TMB-Hi, P = 0.047; TMB-Lo, P = 0.39), and also found to hold true in the more-indolent Luminal A tumor subtype (TMB-Hi, P = 0.011; TMB-Lo, P = 0.91). In TMB-Hi tumors, the FID subclass was associated with prolonged survival independent of tumor stage, molecular subtype, age and treatment. Copy number analysis revealed the reproducible, preferential amplification of chromosome 1q immune-regulatory genes in the PID immune subclass. These findings demonstrate a previously unappreciated role for TMB as a determinant of immune-mediated survival of breast cancer patients and identify candidate immune-regulatory mechanisms associated with immunologically cold tumors. Immune subtyping of breast cancers may offer opportunities for therapeutic stratification.

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T-cell metagene predicts a favorable prognosis in estrogen receptor-negative and HER2-positive breast cancers

Cited by 403 publications

References 55 publications

Mapping spatial heterogeneity in the tumor microenvironment: a new era for digital pathology

Mapping spatial heterogeneity in the tumor microenvironment: a new era for digital pathology

Breast Cancer: Major Risk Factors and Recent Developments in Treatment

Tumor mutational burden is a determinant of immune-mediated survival in breast cancer

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