Immune cytokine receptors

Immune cytokine receptors, such as the Interleukin-2 receptor (IL-2R), Interleukin-12 receptor (IL-12R), and Interleukin-15 receptor (IL-15R), are critical transmembrane proteins that regulate the activation, survival, and proliferation of T lymphocytes and natural killer cells [1][2]. In the context of engineered Tumor-Infiltrating Lymphocyte (TIL) therapy, these receptors are targeted through indirect activation using membrane-bound cytokines (mbCytokines) [3]. This strategy utilizes juxtacrine signaling, where a cytokine is tethered to the TIL surface, allowing it to bind and activate receptors on the same cell (autocrine) or adjacent cells (paracrine) within the tumor microenvironment [1][4]. By localizing cytokine activity to the cell membrane, this approach aims to provide the necessary stimulatory signals for TIL persistence and anti-tumor activity while avoiding the severe systemic toxicities, such as vascular leak syndrome and systemic inflammatory response syndrome, associated with high-dose soluble cytokine administration [3][5]. This therapeutic modality is primarily being developed to treat advanced solid tumors, including melanoma and lung cancer, where traditional TIL therapies often struggle with limited durability [2][3].

Other names

Interleukin receptorsCytokine receptor superfamilymbCytokine targetsMembrane-bound cytokine receptorsTethered cytokine receptors

Juxtacrine activation of cytokine receptors via membrane-tethered ligands to promote autocrine and paracrine signaling.