Effects of durvalumab alone or combined with tremelimumab on preexisting cells in the tumor microenvironment. Effects of durvalumab alone or combined with tremelimumab on preexisting cells in the tumor microenvironment

Immune checkpoint blockade with anti–PD-1/L1 or anti–CTLA-4 therapies has shown promising results across multiple cancer types, but the mechanisms within the tumor microenvironment (TME) have not been fully characterized. We used single-cell RNA sequencing to investigate the effects of anti–PD-L1 monoclonal antibody (mAb) durvalumab (D) alone and combined with an anti–CTLA-4 mAb, tremelimumab (T), on distinct subsets of immune cells. Upon treatment with D or D+T, two NSCLC tumors showed elevated IFNγ responses, although they differed in magnitude of response but differed in other areas. Our results highlight that D and D+T in the TME have some consistent effects across tumors but also exhibit tumor-specific effects depending on composition and functional state of immune cells in the TME at time of treatment. This complex tumor-specific interplay of diverse immune subtypes in the TME is critical to better understand patient response to immunotherapy. Overall design: Two tumors were treated by Durva and Durva+Treme and underwent single cell sequencing. RNA sequencing of 97 advanced-stage non–small-cell lung carcinoma (NSCLC) biopsies from a nonrandomized phase 1b/2 clinical trial (1108/NCT01693562) were profiled to identify expression of genes of interest.