The Emerging Role of LncRNAs in T-Cell Plasticity in Breast Cancer

Despite advances in breast cancer treatment, the number of lives lost each year remains high. One of the significant challenges in treating breast cancer is the highly complex and dynamic tumor microenvironment (TME), which often makes tumors resistant to various kinds of therapies. To overcome this, researchers are tuning and tweaking the body's immune cells, especially T cells and subsets, to clear cancerous cell residues more effectively from the patient's body. Recent research shows that long non-coding RNAs (lncRNAs), once considered "junk" DNA, play an essential role in shaping T cells' plasticity in healthy and cancerous tissues. In this review, we presented and discussed our perspectives on how specific lncRNAs control T-cell infiltration into tumors and how they contribute to immune escape. For example, LINC00472, MIAT, HITT, NKILA, and MALAT1 influence how T cells enter tumors, while SNHG1, TINCR, and GATA3-AS1 help cancer cells hide from immune attack. These lncRNAs can shift the balance between regulatory T cells (Tregs) and cytotoxic T cells (CTLs), either slowing tumor growth or helping cancer evade destruction by recruiting Tregs, M2 macrophages, and myeloid-derived suppressor cells (MDSCs). LncRNAs regulate key signalling pathways such as NF-κB, Wnt/β-catenin, PI3K/AKT, and JAK/STAT, often by acting as "sponges" for miRNAs that regulate immune checkpoints like PD-L1. Further, LncRNAs are found to remodel cytokine and chemokine networks, ultimately reshaping the TME. Overexpression of lncRNA, such as TINCR and MIAT, GATA3-AS1, leads to enhanced PD-L1 deubiquitination, thus aiding in tumor immune evasion. Moreover, our in silico analysis suggests that lncRNAs modulate various immune-related signaling pathways in T cells. Together, these insights reveal how lncRNAs could be harnessed to fine-tune T-cell plasticity, paving the way for more personalized immunotherapies and improving outcomes for breast cancer patients.