PD-L1 deletion or blockade intrinsically reduces macrophage CD80 levels
Abstract
IntroductionMacrophages in the tumor microenvironment are known to upregulate PD-L1 expression, thereby suppressing T cells through PD-1 ligation. However, the manner in which PD-L1 expression intrinsically impacts macrophages and their immunomodulatory phenotype is less clear. Clarifying this knowledge gap may provide further insight into macrophage function within the tumor microenvironment.MethodsTo characterize the macrophage intrinsic role of PD-L1, we used complementary genetic and pharmacological approaches by analyzing primary murine bone marrow-derived macrophages (BMDMs) with complete genetic PDL1 deletion and wildtype BMDMs treated with anti-PD-L1 blocking antibodies. Macrophages were evaluated in vitro across naïve, pro-inflammatory, and tumor conditioned polarization states. ResultsUnlike prior reports, neither genetic deletion nor antibody blockade dramatically altered the expression of macrophage polarization markers or in vitro phagocytic capacity. However, both conditions consistently and robustly reduced surface levels of a costimulatory molecule, CD80. Reduced CD80 levels prompted further analysis of T cell interacting and antigen presentation associated surface proteins, in which we revealed disparate effects of expression in response to PD-L1 genetic deletion and antibody blockade.DiscussionCollectively, these findings suggest that loss of macrophage PD-L1 reduces CD80 expression and regulates immunoregulatory surface protein expression in vitro.
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BibTeX
@article{waddell2026pdl1,
title = {{PD-L1 deletion or blockade intrinsically reduces macrophage CD80 levels}},
author = {Trinity Waddell and Haidong Dong and Minna Roh-Johnson and Jessica N. Lancaster},
journal = {Frontiers in Oncology},
year = {2026},
month = oct,
doi = {10.3389/fonc.2026.1917545},
url = {https://www.frontiersin.org/articles/10.3389/fonc.2026.1917545},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - PD-L1 deletion or blockade intrinsically reduces macrophage CD80 levels
AU - Trinity Waddell
AU - Haidong Dong
AU - Minna Roh-Johnson
AU - Jessica N. Lancaster
PY - 2026
DA - 2026/10/30
JO - Frontiers in Oncology
DO - 10.3389/fonc.2026.1917545
UR - https://www.frontiersin.org/articles/10.3389/fonc.2026.1917545
AB - IntroductionMacrophages in the tumor microenvironment are known to upregulate PD-L1 expression, thereby suppressing T cells through PD-1 ligation. However, the manner in which PD-L1 expression intrinsically impacts macrophages and their immunomodulatory phenotype is less clear. Clarifying this knowledge gap may provide further insight into macrophage function within the tumor microenvironment.MethodsTo characterize the macrophage intrinsic role of PD-L1, we used complementary genetic and pharmacological approaches by analyzing primary murine bone marrow-derived macrophages (BMDMs) with complete genetic PDL1 deletion and wildtype BMDMs treated with anti-PD-L1 blocking antibodies. Macrophages were evaluated in vitro across naïve, pro-inflammatory, and tumor conditioned polarization states. ResultsUnlike prior reports, neither genetic deletion nor antibody blockade dramatically altered the expression of macrophage polarization markers or in vitro phagocytic capacity. However, both conditions consistently and robustly reduced surface levels of a costimulatory molecule, CD80. Reduced CD80 levels prompted further analysis of T cell interacting and antigen presentation associated surface proteins, in which we revealed disparate effects of expression in response to PD-L1 genetic deletion and antibody blockade.DiscussionCollectively, these findings suggest that loss of macrophage PD-L1 reduces CD80 expression and regulates immunoregulatory surface protein expression in vitro.
SN - 2234-943X
ER -