Populations of Triple Negative and Hormone Receptor Positive HER2 Negative Breast Tumors Share Immune Gene Profiles

Frank Schmitz; Wilbert B Copeland; Justine Dell Aringa; Kathryn Newhall; Mary L Disis; Sasha E Stanton*

Frank Schmitz, Wilbert B Copeland, Justine Dell Aringa, Kathryn Newhall, Mary L Disis, and Sasha E Stanton*

Volume5-Issue9
Dates: Received: 2024-09-11 | Accepted: 2024-09-26 | Published: 2024-09-27
Pages: 1200-1213

Abstract

Background: Immune therapy has revolutionized the treatment of certain cancers including melanoma and lung cancer. Breast cancer has fewer tumors with high immune infiltrate and Immune Checkpoint Inhibitor (ICI) therapy has shown the most significant responses in the Triple Negative (TN) subtype although roles are emerging in the other subtypes. The presence of Tumor Infiltrating Lymphocytes (TIL) is predictive of response to ICI therapy in metastatic TN and associated with better survival in local TN disease. Hormone Receptor (HR) positive HER2 negative (HR+HER2-) breast tumors do not show improved prognosis with increasing TIL and only a small portion of HR+HER2- tumors respond to ICI in both metastatic and local disease. We therefore sought to identify genetic differences between TN and HR+HER2- tumors to identify how these may contribute to their differences in immune infiltrate.

Methods: We contrasted immune-associated gene expression between 119 TN and 475 HR+HER2- breast tumors from The Cancer Genome Atlas (TCGA) and confirmed our findings from 299 TN and 1369 HR+HER2- breast tumors in METABRIC.

Results: We found that TN and HR+HER2- tumors can be grouped into immune-high or -low tumors, with both subtypes represented in the immune-high group (40% HR+HER2- tumors of both Luminal A and Luminal B type and 71% TN tumors) in the TCGA. The genes upregulated in the immune-high cluster included GZMB, CXCL9, and IDO1 (Log2FC > 2; Adj. p < 10X10-40). The largest expression difference between the immune-high TN and HR+HER2- tumors was that TN tumors had more abundant Th1 and Th2 CD4+ T cells while HR+HER2- tumors had more abundant fibroblasts (Log2FC > 0.3; Adj p < 10X10-10).

Conclusions: Our data suggest that an immune-high signature is not dictated by breast cancer subtype. However, fibroblasts, particularly fibroblast subsets associated with worse outcome, are more abundant in the immune-high HR+HER2- tumors.

FullText HTML FullText PDF DOI: 10.37871/jbres2008

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How to cite this article

Schmitz F, Copeland WB, Aringa JD, Newhall K, Disis ML, Stanton SE. Populations of Triple Negative and Hormone Receptor Positive HER2 Negative Breast Tumors Share Immune Gene Profi les. J Biomed Res Environ Sci. 2024 Sept 27; 5(9): 1200-1213. doi: 10.37871/jbres2008, Article ID: JBRES2008, Available at: https://www.jelsciences.com/articles/jbres2008.pdf

Subject area(s)

Oncology

Immunology

Cancer

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