CD4 T cell dynamics shape the immune response to combination oncolytic herpes virus and BRAF inhibitor therapy for melanoma.
Galabina BozhanovaJehanne HassanLizzie AppletonVictoria JenningsShane FooMartin McLaughlinCharleen Ml Chan Wah HakEmmanuel C PatinEva Crespo-RodriguezGabby BakerEdward ArmstrongMatthew ChiuHardev PandhaAdel SamsonVictoria RoulstoneJoan KyulaRichard VileFiona Errington-MaisMalin PedersenKevin J HarringtonMasahiro OnoAlan A MelcherPublished in: Journal for immunotherapy of cancer (2022)
Combination HSV/BRAFi is an immunogenic therapy for BRAF mutant melanoma, but cannot fully control tumors. Dual therapy results in changes in T cell dynamics within tumors, with relatively maintained antigen signaling in Treg compared with conv CD4+. Antigen-engaged CD4 +effectors correlate with tumor growth control, and depletion of Treg by addition of an anti-CD25 ICI, releasing suppression of conventional CD4 +effectors by Treg, enhances survival and activates immune signaling within tumors.