1. Immunotherapy Resistance

Despite the enormous success of immune checkpoint blockade (ICB), only a minority of patients with specific cancer types respond to ICB therapy. Predicting ICB response and understanding the resistance mechanisms are still open questions. We designed a transcriptomic signature TIDE (Tumor Immune Dysfunction and Exclusion) that measures the potential of tumor immune evasion as a surrogate biomarker for ICB response (Jiang et al., Nature Medicine, 2018). TIDE can predict the clinical response to both anti-PD1 and anti-CTLA4 therapies with a higher accuracy than other biomarkers such as PD-L1 level and mutation load. TIDE also revealed new candidate ICB resistance regulators, such as SERPINB9, whose activity in cancer cells can resist the T-cell mediated tumor killing. Meanwhile, together with my collaborators, we identified several genes, such as PBRM1, as regulators of tumor immune escape and ICB resistance (Pan et al., Science 2018. Jiang as co-first author).

  • Demonstration of TIDE prediction performance.


  • Graphical Abstract of CRISPR screens to identify regulator genes of T-cell mediated killing.Discovery of genes regulating sensitivity and resistance of tumor cells to T cell-mediated killing