Instruct: Identify the main category of Biorxiv papers based on the titles and abstracts
Query: Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade Immune checkpoint blockade (ICB) has significantly improved the prognosis of cancer patients, but the majority experience limited benefit, evidencing the need for new therapeutic approaches. Upregulation of sialic acid-containing glycans, termed hypersialylation, is a common feature of cancer-associated glycosylation, driving disease progression and immune escape via the engagement of Siglec-receptors on tumor-infiltrating immune cells. Here, we show that tumor sialylation correlates with distinct immune states and reduced survival in human cancers. The targeted removal of Siglec-ligands in the tumor microenvironment, using an antibody-sialidase conjugate, enhances anti-tumor immunity and halts tumor progression in several mouse tumor models. Using single-cell RNA sequencing, we reveal desialylation mechanistically to repolarize tumor-associated macrophages (TAMs) and identify Siglec-E on TAMs as the main receptor for hypersialylation. Finally, we show genetic and therapeutic desialylation, as well as loss of Siglec-E, to synergize with ICB. Thus, therapeutic desialylation represents a novel immunotherapeutic approach, shaping macrophage phenotypes and augmenting the adaptive anti-tumor immune response.
26
The categories of this paper are: biochemistry
7
The categories of this paper are: ecology
28
The categories of this paper are: communication
17
The categories of this paper are: molecular
9
The categories of this paper are: synthetic
27
The categories of this paper are: pathology
1
The categories of this paper are: bioinformatics
31
The categories of this paper are: paleontology
21
The categories of this paper are: toxicology
8
The categories of this paper are: genomics
12
The categories of this paper are: behavior
18
The categories of this paper are: systems
5
The categories of this paper are: cell
19
The categories of this paper are: epidemiology
3
The categories of this paper are: evolutionary
30
The categories of this paper are: scientific