1. (A) (B) Supplementary Figure S1

2. FSC-A Live/Dead CD3 NK1.1 CD4 CD8 4-1BB PD-1 4-1BB PD-1 CD4+CD8+CD3+Live cells (A) Isotype-treated FSC-A Live/Dead CD3 NK1.1 CD4 CD8 4-1BB PD-1 4-1BB PD-1 CD4+CD8+CD3+Live cells (B) Anti-4-1BB-treated Supplementary Figure S2

3. Supplementary Figure S3

4. (A)(B)(C) Supplementary Figure S4

5. Supplementary Figure S5

6. Supplementary Tables Table S1A Incidence and Severity of Microscopic Findings in the Liver Group 1 (PBS), Group 2-4 (0.1, 1, or 5 mg/kg 4-1BB agonist mAb, respectively), Group 5 (20 mg/kg PD- antagonist mAb), Group 6-8 (20 mg/kg PD-1 antagonist mAb plus 0.1, 1, or 5 mg/kg 4-1BB agonist mAb, respectively) mice were euthanized for necropsy and histological analysis 10 days after a single subcutaneous administration. Microscopic findingGroup 1Group 2Group 3Group 4Group 5Group 6Group 7Group 8 Mixed Cell Infiltration3/54/55/5 4/55/5 Minimal34--44-- Mild---2-111 Moderate--53--43 Marked-------1 Single Cell Necrosis0/5 5/5 0/5 5/5 Minimal--53--43 Mild---2--12 Supplementary Table S1A

7. Table S1B Incidence and Severity of Microscopic Findings in the Spleen See Table 1a for group assignments. * Extramedulary hematopoiesis Microscopic FindingsGroup 1Group 2Group 3Group 4Group 5Group 6Group 7Group 8 Lymphoid Hyperplasia1/53/54/5 5/5 Minimal1333331- Mild--112244 Moderate ---1 Increased EMH * 2/5 1/50/55/5 Minimal22211-44 Mild---1--11 Supplementary Table S1B