Targeting toll-like receptors on T cells as a therapeutic strategy against tumors

Innate and adaptive immunity synergistically contribute to an effective anti-tumor response. Therapeutics targeting T cells, such as immune checkpoint inhibitors and engineered chimeric antigen receptor (CAR) T cells have shown promising effects in patients with hematologic malignancies. These strategies aim to strengthen T cell activation, proliferation, survival, and/or effector function by altering T cell receptor (TCR) signaling, co-stimulation, and cytokine gene expression. Toll-like receptors (TLRs) are primarily expressed by innate immune cells and are known to recognize pathogen-associated molecular patterns (PAMPs). However, increasing studies have highlighted their intrinsic contribution to T cell-mediated anti-tumor responses. Here, we have summarized the advances in our understanding of the ability of different types of TLRs and their downstream signaling pathways to activate anti-tumor immunity in T cells. Additionally, we discuss the potential for TLR agonists in improving the therapeutic effects when used in combination with other treatments.