PSGL-1 Shows Promise as Cancer immunotherapy Target

TARGETING the immune regulator PSGL-1 could offer a new approach to cancer immunotherapy, according to a review.

The research examines how P-selectin glycoprotein ligand-1 (PSGL-1), also known as CD162, influences immune responses and cancer behaviour, highlighting its potential as a therapeutic target.

Researchers found that  PSGL-1 antibodies may be broader than previously anticipated, potentially reducing PSGL-1 activity through distinct mechanisms and in more
than one immune cell type.

PSGL-1 represents a promising candidate for next-generation cancer immunotherapy, with potential to stimulate anti-tumor immunity, remodel the tumor microenvironment, and target malignant hematopoietic cell properties.

Regulating Anti-Tumour Immunity

Initially recognised for its role in helping immune cells move through the body, PSGL-1 also regulates their activity.

In cancer models, it can restrain T-cell responses and contribute to exhausted states, supporting its classification as an immune checkpoint-like regulator.

The review describes preclinical findings in which genetic deletion or antibody-mediated blockade of PSGL-1 increased the activity of tumour-infiltrating T cells and encouraged immune-stimulating myeloid-cell behaviour. These changes were associated with reduced tumour growth.

Potential for Combination Treatment

Evidence summarised in the review suggests that targeting PSGL-1 could complement established immunotherapies, including PD-1/PD-L1 blockade and chimeric antigen receptor T-cell therapy.

By influencing several immune-cell populations, this approach could help reshape the tumour microenvironment and strengthen anti-tumour responses.

Relevance to Blood Cancers

PSGL-1 may also provide a direct target in haematological malignancies, where it is often expressed by malignant cells. Its roles include supporting cancer-cell trafficking, tissue dissemination, and resistance to chemotherapy.

Together, these findings identify PSGL-1 as a candidate for further therapeutic development and it could complement current immunotherapies and open new avenues for treating resistant or relapsed cancers.. However, the evidence highlighted is predominantly preclinical: its promise should not be interpreted as established clinical efficacy. Further clinical investigation is needed to determine how these approaches might benefit patients.

Reference

Pereira JL et al. Targeting the PSGL-1 Glycoprotein in Cancer: Cellular Mechanisms and Emerging Immunotherapeutic Strategies. Immunotherapy Advances. 2026;ltag023. doi:10.1093/immadv/ltag023.