Beyond conventional immune checkpoints: the LILRB axis as a dual regulator of tumor and immune cell states.
- 1Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy.
- 2Department of Molecular Biotechnology and Health Sciences, University of Turin, Turin, Italy. [email protected].
- 3Molecular Biotechnology Center "Guido Tarone", University of Turin, Turin, Italy. [email protected].
Abstract
Immune checkpoint blockade targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/PD-L1 has transformed cancer therapy. However, limited response rates and frequent resistance highlight additional mechanisms of immune suppression within the tumor microenvironment (TME), particularly those driven by myeloid and innate immune compartments. The leukocyte immunoglobulin-like receptor B (LILRB) family has emerged as a central regulatory axis integrating immune and tumor cell-intrinsic programs. Beyond restraining immune activation, LILRB receptors reprogram myeloid cells toward tolerogenic states and, when expressed by tumor cells, directly sustain proliferation, metabolic adaptation, angiogenesis, and immune evasion. This dual functionality positions the LILRB axis as a system-level checkpoint linking immune suppression with tumor cell fitness. Here, we synthesize current knowledge on LILRB biology and discuss its implications for cancer immunotherapy, highlighting how targeting this pathway may overcome resistance to PD-1/PD-L1 blockade and enable more effective combination strategies aimed at reprogramming the tumor-immune ecosystem.
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BibTeX
@article{scagliotti2026beyond,
title = {{Beyond conventional immune checkpoints: the LILRB axis as a dual regulator of tumor and immune cell states.}},
author = {Alessandro Scagliotti and Ivan Depetro and Giorgia Tiberi and Paula Ariadna Diez-Villegas and Ermes Candiello and Paola Cappello},
journal = {Journal of experimental \& clinical cancer research : CR},
year = {2026},
month = aug,
doi = {10.1186/s13046-026-03796-2},
url = {https://europepmc.org/article/MED/42958587},
note = {CC BY},
}
RIS
TY - JOUR
TI - Beyond conventional immune checkpoints: the LILRB axis as a dual regulator of tumor and immune cell states.
AU - Alessandro Scagliotti
AU - Ivan Depetro
AU - Giorgia Tiberi
AU - Paula Ariadna Diez-Villegas
AU - Ermes Candiello
AU - Paola Cappello
PY - 2026
DA - 2026/08/01
JO - Journal of experimental & clinical cancer research : CR
DO - 10.1186/s13046-026-03796-2
UR - https://europepmc.org/article/MED/42958587
AB - Immune checkpoint blockade targeting cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1)/PD-L1 has transformed cancer therapy. However, limited response rates and frequent resistance highlight additional mechanisms of immune suppression within the tumor microenvironment (TME), particularly those driven by myeloid and innate immune compartments. The leukocyte immunoglobulin-like receptor B (LILRB) family has emerged as a central regulatory axis integrating immune and tumor cell-intrinsic programs. Beyond restraining immune activation, LILRB receptors reprogram myeloid cells toward tolerogenic states and, when expressed by tumor cells, directly sustain proliferation, metabolic adaptation, angiogenesis, and immune evasion. This dual functionality positions the LILRB axis as a system-level checkpoint linking immune suppression with tumor cell fitness. Here, we synthesize current knowledge on LILRB biology and discuss its implications for cancer immunotherapy, highlighting how targeting this pathway may overcome resistance to PD-1/PD-L1 blockade and enable more effective combination strategies aimed at reprogramming the tumor-immune ecosystem.
SN - 0392-9078
SN - 1756-9966
ER -