Predicting response to epigenetic drug therapy
The present invention relates to the field of epigenetics. More specifically, the present invention provides methods and compositions useful for predicting response to epigenetic drug therapy. As described herein, we have identified a unique signature termed AZA Immune gene set or AIM that differentiates patients with a low immune and high immune signature and is regulated by epigenetic drugs such as demethylating drugs, histone deacetylase inhibitors. In certain embodiments, patients with a high immune signature may benefit from immunotherapies such as anti PD1 or anti PDL1 antibodies or vaccines. In other embodiments, patients with a low immune signature or low AIM would be patients who would then benefit from treatment with epigenetic drugs and then subsequent immunotherapy.
1. A method comprising the step of measuring the expression of ISG20, IFI27, ISG15, IRF9, IFITM3, IRF7, IFI44L, IFITM1, OASL, IFI6, OAS2, STAT1, OAS1, MX1, IFIT1, IFI44, IFIH1, MX2 and DDX58 in a biological sample obtained from a human patient having ovarian cancer, wherein the measuring step is accomplished using an array or polymerase chain reaction.
2. The method of claim 1 , wherein the biological sample is a tissue sample.
3. The method of claim 1 , wherein the biological sample is formalin-fixed, paraffin embedded tissue.
4. The method of claim 1 , wherein the PCR is qRT-PCR.
5. A method comprising the steps of:
(a) measuring the expression of ISG20, IFI27, ISG15, IRF9, IFITM3, IRF7, IFI44L, IFITM1, OASL, IFI6, OAS2, STAT1, OAS1, MX1, IFIT1, IFI44, IFIH1, MX2 and DDX58 in a biological sample obtained from a human patient having or suspected of having ovarian cancer, wherein the measuring step is accomplished using an array or polymerase chain reaction;
(b) comparing the expression to a reference of expression levels; and
(c) treating the patient with immunotherapy if the measured expression levels are higher than the reference levels or treating the patient with epigenetic therapy followed by immunotherapy if the measured expression levels are lower than the reference levels.
6. The method of claim 5 , wherein the biological sample is a tissue sample.
7. The method of claim 5 , wherein the biological sample is formalin-fixed, paraffin embedded tissue.
8. The method of claim 5 , wherein the PCR is qRT-PCR.
9. The method of claim 5 , wherein the epigenetic therapy comprises treatment with a DNA methyltransferase inhibitor and/or a histone deactytelase inhibitor.
10. The method of claim 5 , wherein the immunotherapy comprises a checkpoint inhibitor.
11. The method of claim 10 , wherein the checkpoint inhibitor comprises anti PD1 or anti PDL1 antibodies.