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

The tumor necrosis factor-α (TNFα)-induced protein 8-like (TIPE/TNFAIP8) protein family plays a critical role in regulating immune response and tumorigenesis. This family consists of four distinct members: the founding member TNFα-induced protein 8 (TIPE/TNFAIP8), 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 sharing high sequence homology, individual TIPE members mediate context-dependent, diverse biological roles, including the regulation of inflammation, oncogenesis, anti-tumor activities and cell death. In this review, we focus on the oncogenic and immune regulatory roles of TIPE family members within the breast cancer (BC) tumor microenvironment (TME) and thoroughly discuss how these proteins contribute to therapy response in BC patients.