In the TME, the expression of CTLA-4 on T cells, especially Tregs, can be upregulated, resulting in a decline in the activation and proliferation of CTLs that are crucial for recognizing and destroying cancer cells.292,293 For example, a recent study demonstrates that combining radiation therapy and anti-CTLA-4 with an agonistic CD40 antibody can significantly enhance anti-tumor-immune responses in immune checkpoint blockade-refractory TNBC by overcoming CTLA-4-mediated suppression. Here, CD40 is linked to neoplasm.