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 IFN? 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.