Dual phagocytosis-checkpoint blockade revitalizes immune surveillance in mouse models of glioblastoma
Macrophage-mediated phagocytosis of tumor cells elicits potent antitumor immunity. Nonetheless, sole-blockade of the anti-phagocytosis molecule CD47 has yielded insufficient therapeutic outcomes. Here, we report that glioblastoma (GBM) cells expressed abundant levels of phagocytosis checkpoint CD24. We further show that dual blockade of CD24 and CD47 synergistically enhances the pro-phagocytic activity of macrophages, thereby improving tumor antigen cross-presentation and activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway. This innate immune activation facilitates T cell infiltration into tumors and sensitizes tumors to anti-PD1 therapy, improving survival outcomes in murine GBM models, including immunosuppressive tumors reflecting human GBM-like features. Thus, our results indicate that dual-phagocytosis checkpoint blockade offers a promising therapeutic avenue to potentiate cancer immunotherapy.
Authors
- Mylin A. Torres (ORCID: https://orcid.org/0000-0003-3582-5216)
- Maurice Dufilho
- Ian E. McCutcheon (ORCID: https://orcid.org/0000-0002-1638-3400)
- Weiye Deng (ORCID: https://orcid.org/0000-0003-4243-5013)
- Seong Dong Jeong (ORCID: https://orcid.org/0009-0003-5163-3924)
- Chibawanye Ene (ORCID: https://orcid.org/0000-0002-2653-281X)
- Kadir C. Akdemir (ORCID: https://orcid.org/0000-0003-2299-2373)
- Adam Grippin (ORCID: https://orcid.org/0000-0002-8076-4240)
- Vinay K. Puduvalli (ORCID: https://orcid.org/0000-0001-8396-9500)
- Benjamin R. Schrank (ORCID: https://orcid.org/0000-0001-8138-4250)
- Shiyan Dong (ORCID: https://orcid.org/0000-0003-2912-8895)
- Jeffrey S. Weinberg (ORCID: https://orcid.org/0000-0001-5587-6673)
- Sherise Desiree Ferguson (ORCID: https://orcid.org/0000-0002-6344-0615)
- Annette Wu (ORCID: https://orcid.org/0009-0005-8343-4748)
- Sangeeta Goswami (ORCID: https://orcid.org/0000-0001-9201-4503)
- Sonali Jindal (ORCID: https://orcid.org/0000-0002-3911-6815)
- Yifan Ma (ORCID: https://orcid.org/0000-0002-1341-5059)
- Sreyashi Basu (ORCID: https://orcid.org/0000-0002-5028-3833)
- Kristin Michelle Huntoon (ORCID: https://orcid.org/0000-0002-7211-8986)
- Padmanee Sharma
- JongHoon Ha
- Yifan Wang
- Yen-Tzu Chang
- Frederick F. Lang
- Shannon McCabe
- Mengyu Chang
- Jared L. Edwards
- Sujit Prabhu
- Jian Hu
- Xiaotian Wang
- Shaan M. Raza
- Wen Jiang
- Betty Y. S. Kim
- Franco DeMonte
Institutions
- The University of Texas MD Anderson Cancer Center (US)
- University of Arizona (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-03-09
- DOI
- https://doi.org/10.1038/s41467-026-70221-9
- Primary Topic
- Phagocytosis and Immune Regulation
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Break Through Cancer
- National Institutes of Health