CD28 and neoplasm: In addition, the interaction between CTLA-4: B7-1 and CD28: B7 signaling often plays an important role in the early stage of T-cell activation, which weakens, inhibits, and/or abrogates the activation of naive T-cells in the second lymphoid organs (such as lymph nodes), while the high expression of PD-L1 is often specifically limited to tumor cells and immune cells in the tumor microenvironment.