| First Author | Sun F | Year | 2019 |
| Journal | Nat Commun | Volume | 10 |
| Issue | 1 | Pages | 5324 |
| PubMed ID | 31757943 | Mgi Jnum | J:283716 |
| Mgi Id | MGI:6388010 | Doi | 10.1038/s41467-019-13331-x |
| Citation | Sun F, et al. (2019) Causative role of PDLIM2 epigenetic repression in lung cancer and therapeutic resistance. Nat Commun 10(1):5324 |
| abstractText | Most cancers are resistant to anti-PD-1/PD-L1 and chemotherapy. Herein we identify PDLIM2 as a tumor suppressor particularly important for lung cancer therapeutic responses. While PDLIM2 is epigenetically repressed in human lung cancer, associating with therapeutic resistance and poor prognosis, its global or lung epithelial-specific deletion in mice causes increased lung cancer development, chemoresistance, and complete resistance to anti-PD-1 and epigenetic drugs. PDLIM2 epigenetic restoration or ectopic expression shows antitumor activity, and synergizes with anti-PD-1, notably, with chemotherapy for complete remission of most lung cancers. Mechanistically, through repressing NF-kappaB/RelA and STAT3, PDLIM2 increases expression of genes involved in antigen presentation and T-cell activation while repressing multidrug resistance genes and cancer-related genes, thereby rendering cancer cells vulnerable to immune attacks and therapies. We identify PDLIM2-independent PD-L1 induction by chemotherapeutic and epigenetic drugs as another mechanism for their synergy with anti-PD-1. These findings establish a rationale to use combination therapies for cancer treatment. |
