Macrophage M2 polarization markers are downregulated in Basal compared to Luminal A and Luminal B Breast Cancer.

다국어 초록 (Multilingual Abstract)

The basal subtype represents 15–25% of breast cancer cases and is characterized by aggressive behavior and being more common in younger women with a rapidly relapsing outcome. Most of those basal‐like breast cancers are invasive ductal carcinomas that usually are diagnosed later in the course of the disease usually with metastasis to lungs or brains specifically. Interestingly, such a tumor when infiltrated with immune cells showed better prognoses, with or without any treatment. Since the immune system plays a substantial role in promoting progression and metastasis in breast cancer, understanding the type of immune cells infiltrates can lead to a better understanding of the metastatic trends in such aggressive cancer and potentiate proper immunotherapy.
The aim of the present study is to use a publicly available transcriptomic database for proper clustering of breast cancer cases into clear molecular subtypes then estimate the percentage of infiltrating immune cells and it's status of activation or polarization based on the cancer sample transcriptomic profile.
Breast Invasive Carcinoma TCGA PanCancer databases (1,084 breast cancer samples) were used to identify clear molecular subtypes based on their transcriptomic profiling to exclude the ones that are not clustered into a given subtype then match the resulting clustering with the established clinical and pathological diagnosis. AltAnalyze tool was used for unsupervised clustering of samples through the “Unsupervised Single‐Cell Population Identification” platform. The raw mRNA expression of genes that are differentially expressed between the groups were used for in silico prediction of the immune cells' infiltration using CIBERSORT analytical tool.
Three clear molecular subtypes [(basal, n=101), (Luminal A, n=225) and (Luminal B, n=127)] were matching the clinical and pathological diagnosis in the dataset with the highest percentage of the correct assignment within the group where the unsupervised clustering matched the supervised one. Interestingly, the basal subtype showed different percentages of infiltrating immune cells in terms of number and status compared to luminal A and luminal B. Basal subtype showed more M0 and M1 but less M2 macrophage compared to luminal A and B.
Tumor‐associated macrophages (TAM) density correlates with poor prognosis in breast cancer and are of two different polarized phenotypes. Migratory TAM (less M2‐like or M1) that can inhibit cancer progression and the more M2‐like or “trophic” macrophages that can work in favor of the cancer progression. Our results confirm that basal subtypes have a unique preference to M1 like TAM in comparison to luminal A and B. M1 TAM traditionally, exhibit tumoricidal activities under the influence of Th1‐cytokines such as interferon‐γ (IFNγ) or lipopolysaccharide (LPS)secretes cytokines that can result in chronic inflammation and extensive tissue damage.
Our in silico model showed that Basal Breast cancer exhibit M1 TAM enrichment and this can be a potential target therapy in the future for such deadly disease.
Percentage of immune cells infiltration in basal versus luminal A and b breast cancer as predicted by CIBERSORT analytical tool