| First Author | Sun Y | Year | 2021 |
| Journal | Nat Commun | Volume | 12 |
| Issue | 1 | Pages | 5147 |
| PubMed ID | 34446716 | Mgi Jnum | J:327666 |
| Mgi Id | MGI:6762301 | Doi | 10.1038/s41467-021-25417-6 |
| Citation | Sun Y, et al. (2021) PTENalpha functions as an immune suppressor and promotes immune resistance in PTEN-mutant cancer. Nat Commun 12(1):5147 |
| abstractText | PTEN is frequently mutated in human cancers and PTEN mutants promote tumor progression and metastasis. PTEN mutations have been implicated in immune regulation, however, the underlying mechanism is largely unknown. Here, we report that PTENalpha, the isoform of PTEN, remains active in cancer bearing stop-gained PTEN mutations. Through counteraction of CD8(+) T cell-mediated cytotoxicity, PTENalpha leads to T cell dysfunction and accelerates immune-resistant cancer progression. Clinical analysis further uncovers that PTENalpha-active mutations suppress host immune responses and result in poor prognosis in cancer as relative to PTENalpha-inactive mutations. Furthermore, germline deletion of Ptenalpha in mice increases cell susceptibility to immune attack through augmenting stress granule formation and limiting synthesis of peroxidases, leading to massive oxidative cell death and severe inflammatory damage. We propose that PTENalpha protects tumor from T cell killing and thus PTENalpha is a potential target in antitumor immunotherapy. |
