PD-1 Blockade in Solid Tumors with Defects in Polymerase Epsilon.
Benoit RousseauIvan BiècheÉric PasmantNadim HamzaouiNicolas LeulliotLucas MichonAurélien de ReynièsValerie AttignonMichael B FooteJulien Masliah-PlanchonMagali SvrcekRomain CohenVictor SimmetPaule AugereauDavid MalkaAntoine HollebecqueDamien PouesselCarlos Alberto Gomez-RocaRosine GuimbaudAmandine BruyasMarielle GuilletJean-Jacques GrobMuriel DulucSophie CousinChristelle De La FouchardièreAude FlechonFrédéric RollandSandrine HiretEsma Saada-BouzidOlivier BoucheThierry AndréDiane PannierFarid El HajbiStephane Marie OudardChristophe TournigandJean-Charles SoriaStephane ChampiatDrew G GerberDennis StephensMichelle F Lamendola-EsselSteven B MaronBill H DiplasGuillem ArgilésAsha R KrishnanSéverine Tabone-EglingerAnthony FerrariNeil H SegalAndrea CercekNatalie Hoog-LabouretFrederic LegrandClotilde SimonAssia Lamrani-GhaoutiLuis A DiazPierre SaintignySylvie ChevretAurélien MarabellePublished in: Cancer discovery (2022)
POLE proofreading deficiency leads to high tumor mutational burden with high tumor-infiltrating lymphocytes and predicts anti-PD-1 efficacy in mismatch repair-proficient tumors. Conversely, tumors harboring POLE mutations not affecting proofreading derived no benefit from PD-1 blockade. POLE proofreading deficiency is a new tissue-agnostic biomarker for cancer immunotherapy. This article is highlighted in the In This Issue feature, p. 1397.