Advanced search
Start date

Characterization of molecular pathways associated with the type I IFN response in LAP-deficient macrophages in the context of efferocytosis

Grant number: 22/14525-7
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2023
Effective date (End): August 31, 2026
Field of knowledge:Biological Sciences - Immunology - Cellular Immunology
Principal Investigator:Larissa Dias da Cunha
Grantee:Daniel Leonardo Alzamora Terrel
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated research grant:18/25559-4 - Molecular mechanisms of LC3-associated phagocytosis and its role in macrophage function, AP.JP


The elimination of apoptotic cells (efferocytosis) is an essential mechanism of innate immunity to suppress potential pro-inflammatory responses in different tissues of the body. During efferocytosis, the LC3-associated phagocytosis (LAP) pathway is induced in macrophages, recruiting canonical autophagy components and specific components of the LAP pathway to conjugate the LC3 protein on the phagosome membrane. In this scenario, LAP regulates phagolysosomal maturation and subsequent signaling, dependent on the phagocytosed cargo. In the case of the internalization of apoptotic cells, LAP promotes the anti-inflammatory function of macrophages. During tumor development, these immunosuppressive responses promote cancer progression. On the other hand, defects in the LAP machinery delay tumor growth. In heterotopic graft murine tumor models, antitumor immunity caused by the absence of LAP in myeloid cells requires STING-dependent production of type I IFN in tumor-associated macrophages (TAMs). This evidence suggests that LAP can integrate efferocytosis and signals from the tumor microenvironment in the regulation of gene expression and functional polarization of macrophages towards an anti-inflammatory profile. In this context, alterations in the LAP pathway and STING activation may induce pro-inflammatory responses that allow the reactivation of immunity against cancer cells in the tumor microenvironment. Therefore, in this research project, we intend to investigate the mechanisms of STING activation in macrophages deficient in components of the LAP pathway. This knowledge will be applied in a murine model to explore whether modulation of the LAP pathway and potential activation of STING in the tumor microenvironment can act synergistically with other forms of treatment, such as radiotherapy or immunotherapy, to increase the effectiveness of the antitumor response.

News published in Agência FAPESP Newsletter about the scholarship:
Articles published in other media outlets (0 total):
More itemsLess items

Please report errors in scientific publications list by writing to: