Predicting response to pd-1 axis inhibitors

Abstract

The invention is concerned with a method of predicting response to a PD-1 axis inhibitor such as anti-PD-L1 antibody by determining the abundance of dendritic cells (DCs) in a tumor tissue sample. The abundance of DCs characterized by enhanced expressions of XCR1, IRF8, BATF3 and FLT3 predicts clinical response to the PD-L1 blockade treatment.

1 - 19 . (canceled) 
     
     
         20 . A method for treating a patient with renal cell carcinoma (RCC), the method comprising:
 (i) determining in vitro a dendritic cell (DC) -related gene signature expression level in a tumor tissue sample obtained from the patient, wherein the DC-related gene signature expression level is characterized by an expression level of at least one gene selected from the group consisting of a X-C Motif Chemokine Receptor 1 gene (XCR1), an Interferon Regulatory Factor 8 gene (IRF8), a Basic Leucine Zipper ATF-Like Transcription Factor 3 gene (BATF3) and a FMS Related Receptor Tyrosine Kinase 3 gene (FLT3);   (ii) comparing the DC-related gene signature expression level to a reference DC-related gene signature expression level that is a median DC-related gene signature expression level from a population of RCC patients, and   (iii) if the DC-related gene expression level is above the reference DC-related gene signature expression level, treating the patient with a therapy comprising an effective amount of atezolizumab, wherein the tumor tissue sample is obtained from the patient before the therapy.   
     
     
         21 . The method of  claim 20 , wherein the DC-related gene signature expression level is characterized by an expression level of XCR1. 
     
     
         22 . The method of  claim 20 , wherein the DC-related gene signature expression level is characterized by an expression level of IRF8. 
     
     
         23 . The method of  claim 20 , wherein the DC-related gene signature expression level is characterized by an expression level of XCR1 and IRF8. 
     
     
         24 . The method of  claim 20 , wherein the DC-related gene signature expression level is characterized by an expression level of XCR1, IRF8, BATF3 and FLT3. 
     
     
         25 . The method of  claim 20 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing. 
     
     
         26 . The method of  claim 21 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing. 
     
     
         27 . The method of  claim 23 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing. 
     
     
         28 . The method of  claim 24 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing. 
     
     
         29 . The method of  claim 25 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing. 
     
     
         30 . The method of  claim 20 , wherein the patient is a Programmed death-ligand 1 + (PD-L1+) patient. 
     
     
         31 . The method of  claim 21 , wherein the patient is a PD-L1+ patient. 
     
     
         32 . The method of  claim 23 , wherein the patient is a PD-L1+ patient. 
     
     
         33 . The method of  claim 24 , wherein the patient is a PD-L1+ patient. 
     
     
         34 . The method of  claim 25 , wherein the patient is a PD-L1+ patient. 
     
     
         35 . The method of  claim 20 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing and the patient is a PD-L1+ patient. 
     
     
         36 . The method of  claim 21 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing and the patient is a PD-L1+ patient. 
     
     
         37 . The method of  claim 23 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing and the patient is a PD-L1+ patient. 
     
     
         38 . The method of  claim 24 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing and the patient is a PD-L1+ patient. 
     
     
         39 . The method of  claim 25 , wherein the DC-related gene signature expression level is determined in the sample by RNA sequencing and the patient is a PD-L1+ patient.