| First Author | Strait AA | Year | 2021 |
| Journal | Commun Biol | Volume | 4 |
| Issue | 1 | Pages | 1005 |
| PubMed ID | 34433873 | Mgi Jnum | J:314251 |
| Mgi Id | MGI:6765869 | Doi | 10.1038/s42003-021-02522-2 |
| Citation | Strait AA, et al. (2021) Distinct immune microenvironment profiles of therapeutic responders emerge in combined TGFbeta/PD-L1 blockade-treated squamous cell carcinoma. Commun Biol 4(1):1005 |
| abstractText | Transforming growth factor beta (TGFbeta) and programmed death-ligand 1 (PD-L1) are often overproduced in refractory squamous cell carcinoma (SCC). We examined spatial patterns of PD-L1(+) cells in mouse and human SCCs and found that PD-L1 was primarily expressed on infiltrating leukocytes. Although combined TGFbeta and PD-L1 blockade are undergoing cancer clinical trials, there are no predictive markers for therapeutic responders. To address this, we used both a small molecule TGFbeta inhibitor in combination with anti-PD-L1 and a bifunctional fusion protein targeting both TGFbeta and PD-L1 to treat mouse SCCs and found TGFbeta inhibition enhanced PD-L1 blockade-induced tumor eradication in multiple tumor models. Furthermore, we identified distinct cell populations of responders and non-responders to bintrafusp alfa, with responders showing a shift toward a more immune-permissive microenvironment. The cellular and molecular signatures of responders versus non-responders to combined TGFbeta and PD-L1 blockade provide important insights into future personalized immunotherapy in SCC. |
