While targeting LILRB4 to overcome Tr1-mediated suppression of antitumor immunity shows promise, there are potential limitations and unintended consequences that need to be considered. One limitation is the specificity of targeting LILRB4, as this receptor may have important regulatory functions beyond its role in Tr1 cell-mediated suppression. Blocking LILRB4 could lead to off-target effects or unintended immune dysregulation, impacting the overall immune response. Additionally, the long-term effects of LILRB4 blockade on immune homeostasis and potential autoimmune reactions need to be thoroughly evaluated. Furthermore, the development of resistance mechanisms or compensatory pathways in response to LILRB4 targeting could limit the effectiveness of this approach over time. Careful consideration of these factors is essential to ensure the safety and efficacy of targeting LILRB4 in cancer immunotherapy.