CD122-targeted interleukin-2 and αPD-L1 treat bladder cancer and melanoma via distinct mechanisms, including CD122-driven natural killer cell maturation.

ABSTRACT: Bladder cancer (BC) and melanoma are amenable to immune checkpoint blockade (ICB) therapy, yet most patients with advanced/metastatic disease do not respond. CD122-targeted interleukin (IL)-2 can improve ICB efficacy, but mechanisms are unclear. We tested αPD-L1 and CD122-directed immunotherapy with IL-2/αIL-2 complexes (IL-2c) in primary and metastatic bladder and melanoma tumors. IL-2c treatment of orthotopic MB49 and MBT-2 BC generated NK cell antitumor immunity through enhanced activation, reduced exhaustion, and promotion of a mature, effector NK cell phenotype. By comparison, subcutaneous B16-F10 melanoma, which is IL-2c sensitive, requires CD8⁺ T and not NK cells, yet we found αPD-L1 efficacy requires both CD8⁺ T and NK cells. We then explored αPD-L1 and IL-2c

SUBMITTER: Reyes RM 

PROVIDER: S-EPMC8632314 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature