Supplementary Figures 1 - 16, Table 1, Database 1 from Primary Resistance to PD-1 Blockade Mediated by JAK1/2 Mutations

Supplementary Figure 1. Exome sequencing and copy number changes in M431 and corresponding whole-tumor biopsy. Supplementary Figure 2. Mutations in antigen presentation machinery from anti-PD1 treated melanoma cohort. Supplementary Figure 3. Immunohistochemistry (IHC) analysis of biopsies from melanoma metastases with a JAK1 loss of function mutation. Supplementary Figure 4. Selection of PD-L1 flow cytometry antibody and impact of phosphatase inhibitor as well as temperature on measuring surface PD-L1 expression and pAKT. Supplementary Figure 5. Flow cytometry gating strategy and dose response curve of interferon alpha, beta and gamma to determine the optimal concentrations. Supplementary Figure 6. Time course of PD-L1 surface expression upon interferon alpha, beta and gamma treatment for selected cell lines to determine the optimal time point for the screening. Supplementary Figure 7. Time course of PD-L1 expression upon interferon alpha, beta or gamma treatment for the cell lines with poor or no up-regulation upon 18 hours exposure. Supplementary Figure 8. Interferon signaling pathway in good and poorly responding cell lines. Supplementary Figure 9. PD-L1 expression upon interferon alpha and beta exposure. Supplementary Figure 10. Predicted functional consequences of M368 JAK2 D313 splice site mutation. Supplementary Figure 11. Immunohistochemistry (IHC) analysis of biopsies from melanoma metastases with a JAK1 loss of function mutation. Supplementary Figure 12. JAK1 wild-type lentiviral vector transduction. Supplementary Figure 13. Mutations in antigen presentation machinery from anti-PD1 treated colorectal cohort. Supplementary Figure 14. DNA damage repair gene mutations in endometrial cancer cell lines with JAK1/2 mutations. Supplementary Figure 15. Frequency of JAK1 and JAK2 alterations and their association with overall survival in additional TCGA datasets. Supplementary Figure 16. Functional effect of genetic loss of reactive PD-L1 on responses to PD-1 blockade. Supplementary Database 1. Whole exome sequencing of 23 baseline biopsies from patients analyzed in Fig. 1, and whole exome sequencing of the M431 cell line (Accession code: SRP067938).