4 1BB Agonism Combined With PD L1 Blockade Increases the Number of Tissue Resident CD8+ T Cells and Facilitates Tumor Abrogation
Although the milestone discovery of immune checkpoint blockade (ICB) has been translated into clinical practice, only a fraction of patients can benefit from it with durable responses and subsequent long term survival. Here, we tested the anti tumor effect of combining PD L1 blockade with 4 1BB costimulation in 3LL and 4T1.2 murine tumor models. Dual treatment induced further tumor regression and enhanced survival in tumor bearing mice more so than PD L1 and 4 1BB mAb alone. It was demonstrated that dual anti PD L1/anti 4 1BB immunotherapy increased the number of intratumoral CD103+CD8+ T cells and altered their distribution. Phenotypically, CD103+CD8+ T cells expressed a higher level of 4 1BB and PD 1 than their CD103 counterparts. Administration of PD L1 mAb and 4 1BB mAb further increased the cytolytic capacity of CD103+CD8+ T cells. In vivo, CD103 CD8+ T cells could differentiate into CD103+CD8+ progeny cells. In a human setting, more CD8+ T cells differentiated into CD103+CD8+ T cells in the peripheral tumor region of lung cancer tissues than in the central tumor region. Collectively, infiltrated CD103+CD8+ T cells served as a potential effector T cell population. Combining 4 1BB agonism with PD L1 blockade could increase tumor infiltrated CD103+CD8+T cells, thereby facilitating tumor regression.
Frontiers in Immunology