Enhanced glutamine uptake influences composition of immune cell infiltrates in breast cancer

Ansari, Rokaya El; Craze, Madeleine L; Althobiti, Maryam; Alfarsi, Lutfi; Ellis, Ian O; Rakha, Emad A; Green, Andrew R.

Abstract

Background: Cancer cells must alter their metabolism to support proliferation. Immune evasion also plays a role in supporting tumour progression. This study aimed to find whether enhanced glutamine uptake in breast cancer (BC) can derive the existence of specific immune cells subtypes, including the subsequent impact on patient outcome.

Method: SLC1A5, SLC7A5, SLC3A2 and immune cell markers; CD3, CD8, FOXP3, CD20 and CD68, in addition to PD1 and PDL1 were assessed using immunohistochemistry on TMAs constructed from a large BC cohort (n=803). Patients were stratified based on SLC protein expression into accredited clusters and correlated with immune cell infiltrates and patient outcome. The effect of transient siRNA knockdown of SLC7A5 and SLC1A5 on PDL1 expression was evaluated in MDA-MB-231 cells.

Results: High SLCs were significantly associated with PDL1 and PD1+, FOXP3+, CD68+ and CD20+ cells (p

Citation

Ansari, R. E., Craze, M. L., Althobiti, M., Alfarsi, L., Ellis, I. O., Rakha, E. A., & Green, A. R. (2019). Enhanced glutamine uptake influences composition of immune cell infiltrates in breast cancer. British Journal of Cancer, 122(1), 94–101. https://doi.org/10.1038/s41416-019-0626-z

• Journal Article Type: Article
• Acceptance Date: Oct 21, 2019
• Online Publication Date: Dec 10, 2019
• Publication Date: Dec 10, 2019
• Deposit Date: Jul 8, 2019
• Publicly Available Date: Jun 11, 2020
• Journal: British Journal of Cancer
• Print ISSN: 0007-0920
• Electronic ISSN: 1532-1827
• Publisher: Cancer Research UK
• Peer Reviewed: Peer Reviewed
• Volume: 122
• Issue: 1
• Pages: 94–101
• DOI: https://doi.org/10.1038/s41416-019-0626-z
• Keywords: SLC1A5; SLC7A5; SLC3A2; Breast cancer; Immune cells infiltrates
• Public URL: https://nottingham-repository.worktribe.com/output/2285649
• Publisher URL: https://www.nature.com/articles/s41416-019-0626-z
• Additional Information: Received: 29 April 2019; Revised: 8 July 2019; Accepted: 21 October 2019; First Online: 10 December 2019; : The authors declare no competing interests.; : This study was approved by the Nottingham Research Ethics Committee 2 under the title ‘Development of a molecular genetic classification of breast cancer’ and the North West–Greater Manchester Central Research Ethics Committee under the title ‘Nottingham Health Science Biobank (NHSB)’ reference number 15/NW/0685. The study was performed in accordance with the Declaration of Helsinki.; : Sources of study funding are the University of Nottingham (Nottingham Life Cycle 6 and Cancer Research Priority Area).; : Not applicable.; : The data sets generated during this study are available from the corresponding author on reasonable request.
• Contract Date: Jul 8, 2019