Methods for predicting the survival time of a patient suffering from a solid cancer

Abstract

The present invention provides methods and kits for the prognosis of survival time of a patient suffering from a cancerous tumor. The method involves quantitating the density of Th17 cells at the center of the tumor and at the invasive margin of the tumor, where low density values at each location indicate a favourable prognosis, high values at each location indicate an unfavourable prognosis, and heterogeneous values at the two locations (one high, one low) indicate an intermediate prognosis.

1 . An in vitro method for the prognosis of survival time of a patient suffering from cancer, comprising the steps of:
 a) measuring i) a center (CT) density of Th17 cells in a tumor tissue sample from the center of a tumor from said patient and ii) an invasive margin (IM) density of Th17 cells in a tumor tissue sample from the invasive margin of said tumor;   b) comparing i) said CT density to a predetermined CT density reference value and ii) said IM density to a predetermined IM density reference value; and   c) providing a favorable prognosis of survival time for said patient when said CT density is lower than said predetermined CT density reference value and said IM density is lower than said predetermined IM density reference value; or   providing an unfavorable prognosis of survival time for said patient when said CT density is higher than said predetermined CT density reference value and said IM density is higher than said predetermined IM density reference value.   
     
     
         2 . The in vitro method according to  claim 1 , further comprising the step of
 providing an intermediate prognosis of survival time for said patient when one of said CT density and said IM density is higher and the other of said CT density and said IM density is lower than a corresponding density reference value.   
     
     
         3 . The in vitro method according to  claim 1 , wherein step a) is performed by immunodetection. 
     
     
         4 . The in vitro method according to  claim 1 , wherein the cancer is colorectal cancer. 
     
     
         5 . The in vitro method according to  claim 1 , wherein the survival time is disease-free survival (DFS). 
     
     
         6 . The in vitro method according to  claim 1 , wherein the survival time is overall survival (OS). 
     
     
         7 . The in vitro method according to  claim 1 , further comprising the steps of: i) measuring a CT density and an IM density of at least one additional type of cell; ii) comparing said CT density and said IM density of at least one additional type of cell to corresponding predetermined CT density reference values and iii) using results obtained in said step of comparing to confirm or further refine said favorable prognosis, said unfavorable prognosis or said intermediate prognosis. 
     
     
         8 . The method of  claim 7 , wherein said at least one additional type of cell is selected from the group consisting of cytotoxic T cells, CD3 cells and GZMB cells. 
     
     
         9 . The method of  claim 8 , wherein said at least one additional type of cell is cytotoxic T cells. 
     
     
         10 . The method of  claim 1 , further comprising the step of, if an unfavorable prognosis of survival time for said patient is provided, then concluding that said patient should undergo aggressive adjunct therapy. 
     
     
         11 . The method of  claim 10 , wherein said aggressive adjunct therapy is chemotherapy. 
     
     
         12 . A kit for carrying out the method of  claim 1 , said kit comprising
 at least one agent for detecting Th17 cells in a tumor sample; and   instructions for carrying out the method of  claim 1 .   
     
     
         13 . The kit of  claim 12 , wherein said at least one agent is an antibody. 
     
     
         14 . An in vitro method for determining the efficacy of a cancer treatment in a patient in need thereof, comprising the steps of:
 I) before said cancer treatment is administered to said patient, determining a first prognosis of survival time for said patient by   a) measuring i) a center (CT) density of Th17 cells in a tumor tissue sample from the center of a tumor from said patient and ii) an invasive margin (IM) density of Th17 cells in a tumor tissue sample from the invasive margin of said tumor;   b) comparing i) said CT density to a predetermined CT density reference value and ii) said IM density to a predetermined IM density reference value; and   c) providing a favorable prognosis of survival time for said patient when said CT density is lower than said predetermined CT density reference value and said IM density is lower than said predetermined IM density reference value; or   providing an unfavorable prognosis of survival time for said patient when said CT density is higher than said predetermined CT density reference value and said IM density is higher than said predetermined IM density reference value;   II) after said cancer treatment has been administered to said patient, repeating steps a) to e) in order to determine at least one subsequent prognosis of survival time for said patient;   III) comparing said at least one subsequent prognosis of survival time to said first prognosis of survival time and,   IV) concluding that said treatment is efficacious if said at least one subsequent prognosis of survival time is greater than said first prognosis of survival time, or   concluding that said treatment is not efficacious if said at least one subsequent prognosis of survival time is the same or less than said first prognosis of survival time.   
     
     
         15 . The method of  claim 14 , further comprising the step of repeating steps H to IV over a period of time sufficient to monitor said efficacy of said cancer treatment in said patient. 
     
     
         16 . An in vitro method for determining whether or not a cancer patient is a good candidate for receiving a cancer treatment regimen, comprising the steps of:
 I) determining a first prognosis of survival time for said patient by   a) measuring i) a center (CT) density of Th17 cells in a tumor tissue sample from the center of a tumor from said patient and ii) an invasive margin (IM) density of Th17 cells in a tumor tissue sample from the invasive margin of said tumor;   b) comparing i) said CT density to a predetermined CT density reference value and ii) said IM density to a predetermined IM density reference value; and   c) providing a favorable prognosis of survival time for said patient when said CT density is lower than said predetermined CT density reference value and said IM density is lower than said predetermined IM density reference value; or   providing an unfavorable prognosis of survival time for said patient when said CT density is higher than said predetermined CT density reference value and said IM density is higher than said predetermined IM density reference value;   II) after an initial round of said cancer treatment regimen has been administered to said patient, repeating steps a) to c) in order to determine a second prognosis of survival time for said patient;   III) comparing said second prognosis of survival time to said first prognosis of survival time and,   IV) concluding that said patient is a good candidate for receiving said complete cancer treatment regimen if said second prognosis of survival time is improved compared to said first prognosis of survival time, or   concluding that said patient is not a good candidate for receiving said complete cancer treatment regimen if said second prognosis of survival time is not improved compared to said first prognosis of survival time.   
     
     
         17 . The method of  claim 16 , wherein said cancer treatment regimen is treatment using an immunotherapy agent. 
     
     
         18 . An in vitro method for the prognosis of survival time of a patient suffering from cancer, comprising the steps of:
 a) measuring i) a center (CT) density of CD8 cells in a tumor tissue sample from the center of a tumor from said patient and ii) an invasive margin (IM) density of CD8 cells in a tumor tissue sample from the invasive margin of said tumor;   b) comparing i) said CT density to a predetermined CT density reference value and ii) said IM density to a predetermined IM density reference value; and   c) providing a favorable prognosis of survival time for said patient when said CT density is higher than said predetermined CT density reference value and said IM density is higher than said predetermined IM density reference value; or   providing an unfavorable prognosis of survival time for said patient when said CT density is lower than said predetermined CT density reference value and said IM density is lower than said predetermined IM density reference value; or   providing an intermediate prognosis of survival time for said patient when one of said CT density and said IM density is higher and the other of said CT density and said IM density is lower than a corresponding density reference value; and   when an intermediate prognosis of survival time is indicated, resolving said intermediate prognosis of survival by   a) measuring i) a center (CT) density of Th17 cells in a tumor tissue sample from the center of a tumor from said patient and ii) an invasive margin (IM) density of Th17 cells in a tumor tissue sample from the invasive margin of said tumor;   b) comparing i) said CT density to a predetermined CT density reference value and ii) said IM density to a predetermined IM density reference value; and   c) providing a favorable prognosis of survival time for said patient when said CT density is lower than said predetermined CT density reference value and said IM density is lower than said predetermined IM density reference value; or   providing an unfavorable prognosis of survival time for said patient when said CT density is higher than said predetermined CT density reference value and said IM density is higher than said predetermined IM density reference value.