Loss of IFN-γ Pathway Genes in Tumor Cells as a Mechanism of Resistance to Anti-CTLA-4 Therapy

UCLA study finds why some cancers stop responding to immunotherapy
Better understanding of the steps in the immune response to specific tumour cells will allow for smarter (less trial-&-error), more effective and more individualised combination immunotherapy.
For example, combination of checkpoint inhibitors similarly involved in T-cell activation and survival (eg anti-CTLA4 with anti-PD-1) may give rise to more autoimmune toxicity without a commensurate augmentation in tumour kill. More illogical (and redundant) will be to combine inhibitors targeting the same checkpoint ligation (eg anti-PD-1 with anti-PD-L1).
Instead, combining a checkpoint inhibitor involved in cytotoxic/helper T-cell activation with checkpoint inhibitor involved in regulatory T-cell activation, or with dendritic cell antigen presentation, should be more synergistic. And combining “weaker” checkpoint inhibitors like anti-PD-L1 with anti-TIGIT may deliver better safety without compromising response and survival.