Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021 May 11:12:674192.
doi: 10.3389/fimmu.2021.674192. eCollection 2021.

The Immunology of Hormone Receptor Positive Breast Cancer

Jonathan Goldberg  1 , Ricardo G Pastorello  1   2 , Tuulia Vallius  3 , Janae Davis  1   3 , Yvonne Xiaoyong Cui  1 , Judith Agudo  4   5 , Adrienne G Waks  6 , Tanya Keenan  6 , Sandra S McAllister  7   8   9 , Sara M Tolaney  6 , Elizabeth A Mittendorf  1   2   6   10 , Jennifer L Guerriero  1   2   3   10
Affiliations
Review

The Immunology of Hormone Receptor Positive Breast Cancer

Jonathan Goldberg et al. Front Immunol. .

Abstract

Immune checkpoint blockade (ICB) has revolutionized the treatment of cancer patients. The main focus of ICB has been on reinvigorating the adaptive immune response, namely, activating cytotoxic T cells. ICB has demonstrated only modest benefit against advanced breast cancer, as breast tumors typically establish an immune suppressive tumor microenvironment (TME). Triple-negative breast cancer (TNBC) is associated with infiltration of tumor infiltrating lymphocytes (TILs) and patients with TNBC have shown clinical responses to ICB. In contrast, hormone receptor positive (HR+) breast cancer is characterized by low TIL infiltration and minimal response to ICB. Here we review how HR+ breast tumors establish a TME devoid of TILs, have low HLA class I expression, and recruit immune cells, other than T cells, which impact response to therapy. In addition, we review emerging technologies that have been employed to characterize components of the TME to reveal that tumor associated macrophages (TAMs) are abundant in HR+ cancer, are highly immune-suppressive, associated with tumor progression, chemotherapy and ICB-resistance, metastasis and poor survival. We reveal novel therapeutic targets and possible combinations with ICB to enhance anti-tumor immune responses, which may have great potential in HR+ breast cancer.

Keywords: T-cell exclusion; antigen presentation; breast cancer; clinical trial; hormone receptor (HR); immune exclusion; immunotherapy.

PubMed Disclaimer

Conflict of interest statement

EM has been compensated for participation on Scientific Advisory Boards for Astra-Zeneca/Medimmune, Celgene, Genentech, Exact Sciences (formerly Genomic Health), Merck, Peregrine Pharmaceuticals, SELLAS Lifescience, and Tapimmune and has had clinical trial support to her former institution (M.D. Anderson Cancer Center) from Astra-Zeneca/Medimmune, EMD-Serono, Galena Biopharma and Genentech, and current institution from Genentech via a SU2C grant. EM has also had sponsored Research Support to the laboratory from GSK and Eli Lilly. JG is a consultant for Glaxo-Smith Kline (GSK), Codagenix, Verseau, Kymera and Array BioPharma and receives sponsored research support from GSK, Array BioPharma and Eli Lilly. ST receives institutional research funding from AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Gilead Exelixis, Bristol-Myers Squibb, Eisai, Nanostring, Cyclacel, Odonate, and Seagen; has served as an advisor/consultant to AstraZeneca, Lilly, Merck, Nektar, Novartis, Pfizer, Genentech/Roche, Immunomedics, Bristol-Myers Squibb, Eisai, Nanostring, Seagen, Puma, Sanofi, Celldex, Paxman, Puma, Silverback Therapeutics, G1 Therapeutics, AbbVie, Anthenex, OncoPep, Outcomes4Me, Kyowa Kirin Pharmaceuticals, Daiichi-Sankyo, Gilead and Samsung Bioepsis Inc. AW receives institutional research funding from Genentech/Roche. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Representative images of HR+ breast tumors obtained with highly multiplex cyclic immunofluorescence (CyCIF) imaging (A-C) and the corresponding H&E section (D). CyCIF is a robust tool for the investigation of the complexity of the tumor microenvironment, by linking the cell type with spatial information. (A, B) are from the same formalin-fixed, paraffin embedded (FFPE) slide and (C, D) are both from serial sections of a primary breast tumor (invasive ductal carcinoma, HR+HER2-).
See this image and copyright information in PMC

References

    1. Hargadon KM, Johnson CE, Williams CJ. Immune Checkpoint Blockade Therapy for Cancer: An Overview of FDA-approved Immune Checkpoint Inhibitors. Int Immunopharmacol (2018) 62:29–39. 10.1016/j.intimp.2018.06.001 - DOI - PubMed
    1. Havel JJ, Chowell D, Chan TA. The Evolving Landscape of Biomarkers for Checkpoint Inhibitor Immunotherapy. Nat Rev Cancer (2019) 19(3):133–50. 10.1038/s41568-019-0116-x - DOI - PMC - PubMed
    1. Chan TA, Yarchoan M, Jaffee E, Swanton C, Quezada SA, Stenzinger A, et al. . Development of Tumor Mutation Burden as an Immunotherapy Biomarker: Utility for the Oncology Clinic. Ann Oncol (2019) 30(1):44–56. 10.1093/annonc/mdy495 - DOI - PMC - PubMed
    1. Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, et al. . Mutational Landscape and Significance Across 12 Major Cancer Types. Nature (2013) 502(7471):333–9. 10.1038/nature12634 - DOI - PMC - PubMed
    1. Topalian SL, Taube JM, Anders RA, Pardoll DM. Mechanism-Driven Biomarkers to Guide Immune Checkpoint Blockade in Cancer Therapy. Nat Rev Cancer (2016) 16(5):275–87. 10.1038/nrc.2016.36 - DOI - PMC - PubMed

Publication types

MeSH terms