CTLA4 and cancer: In addition to immunosuppressive cells and cytokines produced in the TME, alternative inhibitory immune checkpoints like TIM-3 and LAG-3 can promote resistance to ICI therapy.131TIM-3 was found to be upregulated on TAM in the TME due to TGF-β exposure,132suggesting an alternative route of checkpoint inhibition used by cancer cells that would not be covered by PD-1/PD-L1 or CTLA-4 ICI therapy.