WNT Signaling in Cancer Immunosurveillance

Deregulated WNT signaling has been shown to favor malignant transformation, tumor progression, and resistance to conventional cancer therapy in a variety of preclinical and clinical settings. Accumulating evidence suggests that aberrant WNT signaling may also subvert cancer immunosurveillance, hence promoting immunoevasion and resistance to multiple immunotherapeutics, including immune checkpoint blockers. Here, we discuss the molecular and cellular mechanisms through which WNT signaling influences cancer immunosurveillance and present potential therapeutic avenues to harness currently available WNT modulators for cancer immunotherapy. Canonical WNT signaling plays a central role in embryogenesis, tissue homeostasis, and wound repair. Deregulated WNT signaling is involved in virtually all stages of oncogenesis. Impaired anticancer immunity as a result of aberrant WNT signaling is emerging as a key contributor to tumor progression and resistance to treatment. Activation of canonical WNT signaling hampers T cell-mediated anticancer immune responses by multiple mechanisms including immune exclusion.