Exploiting the chemokine–chemokine receptor axis: Emerging immunotherapeutic paradigms for solid tumor microenvironment reprogramming

Chemokines play a critical role in regulating immune cell infiltration and their interactions with cancer cells in the tumor microenvironment (TME). Disrupted chemokine gradients influence immune cell recruitment and activation, as well as tumor cell proliferation, metastasis, and angiogenesis. By modulating these processes, chemokines shape the immune landscape of the tumor microenvironment, driving either immunosuppressive or immunostimulatory responses with corresponding pro- or antitumor effects. Dysregulated expression of chemokines and their receptors is strongly associated with tumor initiation, progression, and clinical outcomes. As a result, the chemokine receptor axis has gained prominence as a therapeutic target in cancer immunotherapy. This review explores chemokine expression profiles across various tumor types and their receptor-mediated interactions with immune cells. It also summarizes current strategies to therapeutically target chemokine signaling, both as standalone interventions and in combination with other treatment modalities.