Shruti Malu

TL;DR: A resistance program expressed by malignant cells that is associated with T cell exclusion and immune evasion is identified, and this study provides a high-resolution landscape of ICI-resistant cell states, identifies clinically predictive signatures, and suggests new therapeutic strategies to overcome immunotherapy resistance.

TL;DR: Perturb-CITE-sequencing is developed, enabling pooled clustered regularly interspaced short palindromic repeat-Cas9 perturbations with single-cell transcriptome and protein readouts, and discovers potentially clinically relevant mechanisms of immune evasion.

TL;DR: This work identifies novel mechanisms at the nexus of immune evasion and drug resistance and provides a general framework for deciphering complex mechanisms by large-scale perturbation screens with multi-modal singlecell profiles, including in systems consisting of multiple cell types.

TL;DR: Treatment with the HSP90 inhibitor ganetespib (Synta) greatly improves T cell mediated cytotoxicity of human cancer cells lines in vitro, and in vivo murine studies show that ganestespib in combination with anti-CTLA4, resulted in superior antitumor effect and survival compared to either treatment alone.