TIPE Proteins in Breast Cancer Tumor Microenvironment: Oncogenic Signaling, Immune Modulation, and Therapeutic Implications

The tumor necrosis factor-α (TNFα)-induced protein 8-like (TIPE/TNFAIP8) family plays an important role in regulating tumorigenesis and immune responses. This family comprises four members: the founding member, TNFα-induced protein 8 (TIPE/TNFAIP8), and TNFα-induced protein 8-like 1 (TIPE1/TNFAIP8L1), TNFα-induced protein 8-like 2 (TIPE2/TNFAIP8L2), and TNFα-induced protein 8-like 3 (TIPE3/TNFAIP8L3). Despite their considerable sequence homology, individual TIPE family members exert context-dependent biological functions, including the regulation of inflammation, oncogenesis, antitumor responses, and cell death. TIPE proteins have emerged as important regulators of immune responses and cancer progression; their roles in oncogenic signaling and immune regulation within the breast cancer (BC) tumor microenvironment (TME) remain poorly defined. In this review, we summarize the oncogenic and immunoregulatory functions of TIPE family members within the BC-TME and discuss their contributions to BC progression, tumor–immune interactions, and therapeutic responses. We further highlight the potential of TIPE proteins as biomarkers and therapeutic targets and identify emerging questions regarding their context-dependent functions in BC.