Single cell RNA sequencing of tumors from mice treated with anti-PD-L1 and/or anti-TGFb

The anti-tumor activity of anti-PD-1/PD-L1 therapies correlates with T cell infiltration into tumors. Thus, a major goal in oncology is to find strategies that enhance T cell infiltration and the efficacy of anti-PD-1/PD-L1 therapy. TGFb has been shown to contribute to T cell exclusion and anti-TGFb improved anti-PD-L1 efficacy in vivo. Here we use single-cell RNA-sequencing to characterize the effects of PD-L1 and TGFb blockade on cells in the tumor microenvironment. Anti-PD-L1 plus anti-TGFb led to down-regulation of matrix remodeling associated genes in fibroblasts cells, suggesting the breakdown of a physical barrier to immune infiltration. It also led to enhanced immune responses, including the up-regulation of chemokine genes, prompting us to ask if chemokines may be used to improve immune cell infiltration and control tumor growth. Using computational approaches, we identified CCL5 and CXCL9 to be highly associated with immune cell infiltration in various human cancers. Finally, we found intratumorally administered CCL5 enhances the anti-tumor activity of anti-PD-L1.