AI Article Synopsis
- Cancer cells change their metabolism, particularly through glutamine uptake, to help them grow and evade the immune system, impacting breast cancer progression and patient outcomes.
- The study used tissue samples from 803 breast cancer patients to analyze specific genes related to glutamine transport and immune cell markers, discovering significant correlations with immune cell types and poor patient outcomes.
- Results showed that higher levels of specific glutamine transporters (SLCs) were linked to increased expression of immune markers (like PDL1 and PD1) and that reducing SLC7A5 led to lower PDL1 levels, indicating the role of glutamine pathways in breast cancer and immune responses.
Article 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 cell subtypes, including the subsequent impact on patient outcome.
Methods: SLC1A5, SLC7A5, SLC3A2 and immune cell markers CD3, CD8, FOXP3, CD20 and CD68, in addition to PD1 and PDL1, were assessed by 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 < 0.001). Triple negative (TN), HER2 + and luminal B tumours showed variable associations between SLCs and immune cell types (p ≤ 0.04). The expression of SLCs and PDL1, PD1 +, FOXP3 + and CD68 + cells was associated with poor patient outcome (p < 0.001). Knockdown of SLC7A5 significantly reduced PDL1 expression.
Conclusion: This study provides data that altered glutamine pathways in BC that appears to play a role in deriving specific subtypes of immune cell infiltrates, which either support or counteract its progression.
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Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964696 | PMC |
| http://dx.doi.org/10.1038/s41416-019-0626-z | DOI Listing |
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