In the present study, we show, in an in vivo longitudinal study, that the Slit-Robo pathway is critical for immunosuppressive myeloid cell accumulation in Glioblastoma. Genetic Slit2 depletion in tumor cells leads to cytotoxic myeloid cell accumulation, T-cell enrichment, and normalization of tumor blood vessels, resulting in increased sensitivity to chemotherapy. Administration of systemic Slit2 trap limits glioblastoma progression, demonstrating that the Slit-Robo pathway can be an innovative immunotherapeutic target for the treatment of glioblastoma.
Geraldo LH, Xu Y, Jacob L, Pibouin-Fragner L, Rao R, Maïssa N, Verreault M, Lemaire N, Knosp C, Lesaffre C, Daubon T, Dejaegher J, Solie L, Rudewicz J, Viel T, Tavitian B, De Vleeschouwer S, Sanson M, Bikfalvi A, Idbaih A, Lu QR, Lima FR, Thomas JL, Eichmann A & Mathivet T.:
SLIT2/ROBO signaling in tumor-associated microglia/macrophages drives glioblastoma immunosuppression and vascular dysmorphia
J Clin Invest, 2021