Immunologically "cold" triple negative breast cancers engraft at a higher rate in patient derived xenografts

Varduhi Petrosyan; Lacey E Dobrolecki; Emily L LaPlante; Ramakrishnan Rajaram Srinivasan; Matthew H Bailey; Alana L Welm; Bryan E Welm; Michael T Lewis; Aleksandar Milosavljevic

doi:10.1038/s41523-022-00476-0

Immunologically "cold" triple negative breast cancers engraft at a higher rate in patient derived xenografts

NPJ Breast Cancer. 2022 Sep 10;8(1):104. doi: 10.1038/s41523-022-00476-0.

Authors

Varduhi Petrosyan¹, Lacey E Dobrolecki², Emily L LaPlante¹, Ramakrishnan Rajaram Srinivasan², Matthew H Bailey^{3

4}, Alana L Welm^{4

5}, Bryan E Welm^{4

6}, Michael T Lewis^{2

7

8}, Aleksandar Milosavljevic⁹

Affiliations

¹ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
² Lester and Sue Smith Breast Center, Baylor College of Medicine, Houston, TX, USA.
³ Eccles Institute of Human Genetics, University of Utah, Salt Lake City, UT, USA.
⁴ Huntsman Cancer Institute, University of Utah, Salt Lake City, UT, USA.
⁵ Department of Oncological Sciences, University of Utah, Salt Lake City, UT, USA.
⁶ Department of Surgery, University of Utah, Salt Lake City, UT, USA.
⁷ Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA.
⁸ Departments of Molecular and Cellular Biology and Radiology, Baylor College of Medicine, Houston, TX, USA.
⁹ Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. amilosav@bcm.edu.

Abstract

TNBC is a heterogeneous subtype of breast cancer, and only a subset of TNBC can be established as PDXs. Here, we show that there is an engraftment bias toward TNBC with low levels of immune cell infiltration. Additionally, TNBC that failed to engraft show gene expression consistent with a cancer-promoting immunological state, leading us to hypothesize that the immunological state of the tumor and possibly the state of the immune system of the host may be essential for engraftment.

Grants and funding

U54 CA224076/CA/NCI NIH HHS/United States