4.8 Review

The Immunology of Hormone Receptor Positive Breast Cancer

Journal

FRONTIERS IN IMMUNOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2021.674192

Keywords

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

Categories

Funding

  1. Rob and Karen Hale Distinguished Chair in Surgical Oncology
  2. Dana-Farber/Harvard Cancer Center (DF/HCC) Specialized Program of Research Excellence (SPORE) in Breast Cancer [P50 CA1685404]
  3. Susan G. Komen Foundation Career Catalyst Award [CCR18547597]
  4. Terri Brodeur Breast Cancer Foundation
  5. Saverin Family Foundation at Dana-Farber Cancer Institute
  6. Department of Defense BCRP Era of Hope Expansion Award [W81XWH2010472]
  7. METAvivor Translational Research Award, Chicago Metsquerade Presented in Memory of Lauren Smoke
  8. Finnish Medical Foundation
  9. Relander Foundation
  10. Turku University Foundation
  11. Maud Kuistila Memorial Foundation
  12. Finnish Society of Oncology
  13. Cancer Society of Southwest Finland
  14. Ludwig Center at Harvard
  15. U.S. Department of Defense (DOD) [W81XWH2010472] Funding Source: U.S. Department of Defense (DOD)

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ICB has revolutionized cancer treatment, but has limited efficacy in HR+ breast cancer due to a TME devoid of TILs. TNBC shows clinical responses to ICB due to TIL infiltration, while HR+ breast tumors establish an immune suppressive TME.
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.

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