%0 Journal Article
%T The Importance of HHLA2 in Solid Tumors-A Review of the Literature.
%A Kula A
%A Koszewska D
%A Kot A
%A Dawidowicz M
%A Mielcarska S
%A Waniczek D
%A Świętochowska E
%J Cells
%V 13
%N 10
%D 2024 May 7
%M 38786018
%F 7.666
%R 10.3390/cells13100794
%X Cancer immunotherapy is a rapidly developing field of medicine that aims to use the host's immune mechanisms to inhibit and eliminate cancer cells. Antibodies targeting CTLA-4, PD-1, and its ligand PD-L1 are used in various cancer therapies. However, the most thoroughly researched pathway targeting PD-1/PD-L1 has many limitations, and multiple malignancies resist its effects. Human endogenous retrovirus-H Long repeat-associating 2 (HHLA2, known as B7H5/B7H7/B7y) is the youngest known molecule from the B7 family. HHLA2/TMIGD2/KIRD3DL3 is one of the critical pathways in modulating the immune response. Recent studies have demonstrated that HHLA2 has a double effect in modulating the immune system. The connection of HHLA2 with TMIGD2 induces T cell growth and cytokine production via an AKT-dependent signaling cascade. On the other hand, the binding of HHLA2 and KIR3DL3 leads to the inhibition of T cells and mediates tumor resistance against NK cells. This review aimed to summarize novel information about HHLA2, focusing on immunological mechanisms and clinical features of the HHLA2/KIR3DL3/TMIGD2 pathway in the context of potential strategies for malignancy treatment.