We thus propose a novel therapeutic approach to treating PTCL with alisertib based synergistic combinations that target immune suppression (PD-L1, PI3Kγδ) and proliferation (PI3Kα inhibition, pan-PI3K inhibition and VCR) that could be evaluated in early phase therapeutic trials in PTCL patients relapsing after CHOP-like therapies. This evidence concerns the gene CD274 and mature T-cell and NK-cell non-Hodgkin lymphoma.