Toll-like receptor 4–calreticulin complex (TLR4-CALR complex) (TLR4-CALR complex)

The Toll-like receptor 4–calreticulin (TLR4-CALR) complex is a pivotal immunological assembly that mediates the recognition of dying cells by the innate immune system (Chen et al., Front Oncol, 2021). Calreticulin, normally an endoplasmic reticulum-resident chaperone, translocates to the cell surface (ecto-CRT) during immunogenic cell death (ICD) induced by specific chemotherapeutic agents like anthracyclines or radiation (NIH, 2016). On the surface of immature dendritic cells, TLR4 functions as a receptor for this exposed calreticulin, and their interaction forms a signaling complex that activates the MyD88-dependent pathway (Chen et al., 2021). This activation is essential for the maturation and migration of dendritic cells to secondary lymphoid organs, where they efficiently cross-present tumor antigens to CD8+ T cells (NIH, 2016). By bridging the innate sensing of cellular stress with the activation of adaptive immunity, the TLR4-CALR complex serves as a key determinant of the success of cancer immunotherapies. Therapeutic strategies targeting this complex include the use of ICD-inducing drugs, recombinant calreticulin as an adjuvant, and TLR4 agonists to enhance dendritic cell activation (Chen et al., 2021; NIH, 2012). Monitoring biomarkers such as surface calreticulin expression and dendritic cell infiltration can help predict patient response to these immunotherapeutic approaches.

Other names

TLR4-CRT complexCALR-TLR4 complexCalreticulin-Toll-like receptor 4 complexecto-CRT-TLR4 complex

Induction of calreticulin translocation from the endoplasmic reticulum to the cell surface of stressed or dying cells, where it interacts with TLR4 on dendritic cells to trigger the MyD88-dependent signaling cascade, leading to dendritic cell maturation and anti-tumor immunity.