Multiple factors including constitutive PD-L1 expression in cancer cells, a lack of tumor antigens, defective antigen presentation and processing machinery, the exhaustion of infiltrated T cells, and the presence of an immunosuppressive population—such as Tregs, myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs)—could contribute to acquired resistance to immunotherapy [41,42,43] for TAMs [44]. The gene discussed is CD274; the disease is cancer.