Gupta et al. discover that tumor-initiating cells (TICs) highly expressed PD-L1 in ovarian cancer and melanoma, the intrinsic cell signals produced by PD-L1 promote TIC proliferation and mTORC1 activation, and PD-L1 expression also increases the sensitivity of TIC to IFN-γ and rapamycin, thereby resisting tumor immunotherapy and promoting tumor recurrence [151]. Here, IFNG is linked to melanoma.