SIGLEC1 FACILITATES MACROPHAGE-CD8+ T CELL INTERACTIONS AND CORRELATES WITH CANCER IMMUNOTHERAPY RESPONSE

Authors

Ibanez Molero, S., Coccimiglio, M., Olivia Springer, B., Bowien de Ruiter, M., Clayton, G., Wijnen, S., Blank, C., Labots, M., de Gruijl, T., van Kooyk, Y.

Abstract

Antigen-presenting cell (APC) interactions with cytotoxic T cells are critical for anti-tumour immunity and response to immune checkpoint blockade (ICB), yet context-specific regulators in the tumour microenvironment remain not fully defined. Here we identify the lectin receptor SIGLEC1 as a key mediator of macrophage-T cell interactions in human melanoma. In a well-characterized patient cohort, SIGLEC1 was selectively upregulated in inflammatory macrophages physically associated with activated/exhausted CD8+T cells. Imaging and functional analyses revealed that SIGLEC1 accumulates at the macrophage-T cell interface and promotes cell clustering. SIGLEC1 ligands were enriched on activated T cells, and their blockade reduced cytotoxic cytokine production ex vivo. Single-cell (spatial) transcriptomics across independent ICB-treated melanoma cohorts showed that SIGLEC1+ macrophages localize near CD8+T cells and are enriched in responders, where they also associate with T cells expressing activation/exhaustion markers. These findings define a SIGLEC1-dependent macrophage-T cell niche linked to effective immunotherapy.

Preprint server: bioRxiv
The authors list and abstract were imported from bioRxiv on 16 Jul 2026.

Stats

1-terrible, 9-excellent. How would you rate this preprint? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.