Comparison of tumor microenvironment in primary and paired metastatic ER+/HER2- breast cancers: results of a pilot study

BACKGROUND: Tumor microenvironment (TME) is a dynamic setting and changes in TILs and their subpopulations are potential candidates to influence the metastatic process. Aim of this pilot study is to describe the changes occurring between primary breast cancers and their paired metastases in terms of TILs composition. To assess if these changes influence the process of metastasis development, we used a control group of patients.METHODS: We retrospectively identified 18 Luminal patients, for whom primary and metastatic tissue were available (cases) and 18 paired-matched patients (controls), not relapsed after at least 9years of follow-up, and we quantified TILs and their composition (i.e. T CD8+ and CD4+/FOXP3+). The presence of TILs was defined as ≥10%.RESULTS: Our results showed that the microenvironment composition of relapsed patients was poor of TILs (median=5%, I-III quartiles=0.6-5%), CD8+ (2.5%, 0-5%) and CD4+/FOXP3+(0%, 0-0.6%) in the primary tumor. Comparable results were observed in their related metastases (TILs 3.8%, 0.6-5%; CD8+0%, 0-1.3%; CD4+/FOXP3+0%,0-1.9%). On the contrary, the microenvironment in the control group was richer of TILs (5%, 5-17.5%) in comparison to cases, both in primary tumor (p=0.035) and related metastases (p=0.018). Although CD8+ in controls were similar to cases at primary tumor (p=0.6498), but not at metastasis (p=0.0223), they expressed only one part on the TILs subpopulations (p=0.0060), while TILs in the cases at primary tumor were almost completely CD8+ (p=0.5034).CONCLUSIONS: These findings suggest that the lack of activation of immune system in the primary tumor might influence the multifactor process of cancer progression.