c-Rel is a member of the NF-κB family, predominantly expressed in lymphocytes and myeloid cells. As a transcription factor, it regulates the proinflammatory polarization of myeloid cells and modulates the antitumor immune response. Research has found that c-Rel serves as an important checkpoint for the immunosuppressive function of myeloid-derived suppressor cells (MDSCs). MDSCs hinder the normal function of immune cells in a tumor environment, promoting tumor immune evasion. c-Rel controls the polarization of myeloid cells in tumors, and specific inhibition of c-Rel significantly inhibits tumor growth. In c-Rel-deficient (Rel–/–) mice, melanoma and lymphoma tumor growth was significantly suppressed, with a 80% reduction in tumor size and body weight compared to controls. Inhibiting c-Rel through small molecule inhibitors or conditional knockout in MDSCs can promote the body's antitumor immune response. Combining c-Rel inhibitors with PD-1 functional blocking antibodies can further enhance the activation of the body's antitumor immune response.
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