To demonstrate that ALPN-202 anti-tumor activity is at least partially mediated by PD-L1-dependent CD28 costimulation and is dependent on simultaneous engagement of both PD-L1 and CD28, we treated MC38/hPD-L1 tumor-bearing mice with ALPN-202 alone or in combination with blocking antibodies to mouse CD28 (clone E18) or human PD-L1 (durvalumab). Here, CD28 is linked to neoplasm.