Article Alert: Tumor-associated neutrophils require CD300ld to promote cancer progression

A major factor undermining the clinical efficacy of immunotherapy is the immunosuppressive tumor microenvironment characteristic of many malignancies. Activated tumor-associated neutrophils, also known as polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs), are key players in tumor progression and treatment failure. Destruction of these PMN-MDSCs is therefore a potentially promising strategy to improve patient response to immunotherapeutic regimens.

An exciting study by Wang et al. identifies a pivotal protein on PMN-MDSCs that not only could facilitate targeting of these cells, but is also responsible for their recruitment into tumors and their suppression of T cell activation (1). The authors utilized in vivo CRISPR-Cas9 screening in a tumor mouse model to find that CD300ld, a member of the immunoglobulin receptor superfamily, is upregulated in tumor-associated PMN-MDSCs. CD300ld exerts its effects through the STAT3-S100A8/A9 axis, and knockdown of the protein in PMN-MDSCs inhibits tumor growth by blocking their recruitment to the tumor site and diminishing the tumor microenvironment immunosuppressive milieu. The authors also report that CD300ld expression is elevated in human cancers and negatively impacts patient outcomes. Finally, CD300ld inhibition appears to work synergistically with anti-PD1 therapy. Thus, the work by Wang et al. reveals an intriguing new direction for immunotherapy development.

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