Dual Immunoliposome Targeting of PD-L1 and CSF1R affects T-Cell readouts in tumor-conditioned co-cultures: An In Vitro Study in Glioblastoma and Medulloblastoma
- 1Medical Faculty of University of Duisburg-Essen
Abstract
Glioblastoma and medulloblastoma are characterized by an immunosuppressive tumor microenvironment, in which tumor-associated macrophages may impair T-cell function, in part through the expression of PD-L1 and CSF1R. Single-target therapies have shown inconsistent results in brain tumors, likely due to the complex interplay involving tumor-associated macrophages and immunosuppression. We developed two immunoliposomes functionalized with antibodies against PD-L1 and CSF1R to co-target these receptors on M2-like tumor-associated macrophages. TAM2Ms were generated by polarizing THP-1 monocytes with glioblastoma (A172, U87MG) and medulloblastoma (DAOY, ONS-76) tumor-conditioned medium together with IL-4 and IL-13. In co-culture with activated Jurkat T cells under tumor-conditioned medium-influenced conditions, combined PD-L1 and CSF1R immunoliposomes enhanced T-cell proliferation, reduced apoptosis, and improved migration toward tumor spheroids compared to single-target liposomal treatments or free antibodies. These benefits varied between glioblastoma and medulloblastoma in vitro models, reflecting distinct TAM2M phenotypes and microenvironment contexts. Dual immunoliposome targeting of PD-L1 and CSF1R may offer a promising strategy for reprogramming tumor-associated macrophages in brain tumor immunotherapy and warrants further evaluation in primary human macrophages and in vivo models to clarify efficacy and mechanisms.
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BibTeX
@misc{pour2026dual,
title = {{Dual Immunoliposome Targeting of PD-L1 and CSF1R affects T-Cell readouts in tumor-conditioned co-cultures: An In Vitro Study in Glioblastoma and Medulloblastoma}},
author = {O. Asad Pour and A. Asadpour and J. Ghanam and J. Best and F. Rahbarizadeh and S. Hetze and V. K. Chetty and L. Barthel and Z. Amoozgar and H. H. Schmidt and B. K. Thakur},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.16.751417},
url = {https://www.biorxiv.org/content/10.64898/2026.09.16.751417v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Dual Immunoliposome Targeting of PD-L1 and CSF1R affects T-Cell readouts in tumor-conditioned co-cultures: An In Vitro Study in Glioblastoma and Medulloblastoma
AU - O. Asad Pour
AU - A. Asadpour
AU - J. Ghanam
AU - J. Best
AU - F. Rahbarizadeh
AU - S. Hetze
AU - V. K. Chetty
AU - L. Barthel
AU - Z. Amoozgar
AU - H. H. Schmidt
AU - B. K. Thakur
PY - 2026
DA - 2026/09/16
PB - bioRxiv
DO - 10.64898/2026.09.16.751417
UR - https://www.biorxiv.org/content/10.64898/2026.09.16.751417v1
AB - Glioblastoma and medulloblastoma are characterized by an immunosuppressive tumor microenvironment, in which tumor-associated macrophages may impair T-cell function, in part through the expression of PD-L1 and CSF1R. Single-target therapies have shown inconsistent results in brain tumors, likely due to the complex interplay involving tumor-associated macrophages and immunosuppression. We developed two immunoliposomes functionalized with antibodies against PD-L1 and CSF1R to co-target these receptors on M2-like tumor-associated macrophages. TAM2Ms were generated by polarizing THP-1 monocytes with glioblastoma (A172, U87MG) and medulloblastoma (DAOY, ONS-76) tumor-conditioned medium together with IL-4 and IL-13. In co-culture with activated Jurkat T cells under tumor-conditioned medium-influenced conditions, combined PD-L1 and CSF1R immunoliposomes enhanced T-cell proliferation, reduced apoptosis, and improved migration toward tumor spheroids compared to single-target liposomal treatments or free antibodies. These benefits varied between glioblastoma and medulloblastoma in vitro models, reflecting distinct TAM2M phenotypes and microenvironment contexts. Dual immunoliposome targeting of PD-L1 and CSF1R may offer a promising strategy for reprogramming tumor-associated macrophages in brain tumor immunotherapy and warrants further evaluation in primary human macrophages and in vivo models to clarify efficacy and mechanisms.
ER -