| First Author | Pascual-García M | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 2416 |
| PubMed ID | 31186412 | Mgi Jnum | J:284586 |
| Mgi Id | MGI:6323870 | Doi | 10.1038/s41467-019-10369-9 |
| Citation | Pascual-Garcia M, et al. (2019) LIF regulates CXCL9 in tumor-associated macrophages and prevents CD8(+) T cell tumor-infiltration impairing anti-PD1 therapy. Nat Commun 10(1):2416 |
| abstractText | Cancer response to immunotherapy depends on the infiltration of CD8(+) T cells and the presence of tumor-associated macrophages within tumors. Still, little is known about the determinants of these factors. We show that LIF assumes a crucial role in the regulation of CD8(+) T cell tumor infiltration, while promoting the presence of protumoral tumor-associated macrophages. We observe that the blockade of LIF in tumors expressing high levels of LIF decreases CD206, CD163 and CCL2 and induces CXCL9 expression in tumor-associated macrophages. The blockade of LIF releases the epigenetic silencing of CXCL9 triggering CD8(+) T cell tumor infiltration. The combination of LIF neutralizing antibodies with the inhibition of the PD1 immune checkpoint promotes tumor regression, immunological memory and an increase in overall survival. |
