Infiltration of innate and adoptive lymphoid cells in 4T1 and MC4-L2 breast cancer models.

Abstract

Objectives: Innate lymphoid cells (ILCs) are tissue-resident lymphocytes that have vital roles in activating further immune responses. However, due to their tumor-induced diversity, we decided to examine ILCs, T cells, and the associated cytokines in mouse models of breast cancer.

Materials and methods: 4T1 and MC4-L2 cells were used to induce triple-negative and hormone-receptor-positive breast cancer, respectively. Tumor tissue was resected at early and late stages of tumor growth and used for further analysis. Total RNA was extracted and used in Real-Time PCR to analyze the expression of IFN-γ, IL-4, IL-10, IL-13, and IL-22. Tumor tissue was digested and used in a flow cytometric assay. H&E staining was used to examine the pathology of tumor progression.

Results: Both tumor models showed a notable increase in T-cell frequency at the early stage of tumor growth. However, as the tumors progressed, the frequency of T cells significantly decreased, while the ILC component exhibited a significant increase in tumor progression. Gene analysis indicated a significant increase in the inflammatory to anti-inflammatory cytokine ratio during tumor progression in the tumor model. In contrast, this ratio was considerably reduced in advanced MC4-L2 tumors. Both tumor models showed the development of invasive breast carcinoma and lung metastasis in advanced tumors.

Conclusion: Our study highlighted the expansion of ILCs during tumor progression in two distinct breast cancer models with different immunogenicity. These findings suggest that ILCs may actively modulate the tumor microenvironment during the advanced stage of tumor growth.