USE OF PD-1 AND TIM-3 AS A MEASURE FOR CD8+ CELLS IN PREDICTING AND TREATING RENAL CELL CARCINOMA
The present invention relates to a method for predicting the survival time of a subject suffering from renal cell carcinoma comprising the steps of: i) quantifying the percent of CD8+ T cells co-expressing PD-1 and Tim-3 in a tumor tissue sample obtained from the subject, ii) comparing the percent quantified at step i), with its corresponding predetermined reference value and iii) concluding that the subject will have a short survival time when the percent of CD8+ T cells co-expressing PD-1 and Tim-3 is higher than its corresponding predetermined reference value or concluding that the subject will have a long survival time when the percent of CD8+ T cells co-expressing PD-1 and Tim-3 is lower than its corresponding predetermined reference value.
1 . A method for predicting the survival time of and treating a subject suffering from renal cell carcinoma comprising the steps of:
i) quantifying the percent of CD8+ T cells co-expressing PD-1 and Tim-3 in a tumor tissue sample obtained from the subject,
ii) comparing the percent quantified at step i) with its corresponding predetermined reference value
iii) concluding that the subject will have a short survival time when the percent of CD8+ T cells co-expressing PD-1 and Tim-3 is higher than its corresponding predetermined reference value or concluding that the subject will have a long survival time when the percent of CD8+ T cells co-expressing PD-1 and Tim-3 is lower than its corresponding predetermined reference value; and
iv) administering to a subject with a short survival time a therapeutically effective amount of a treatment that prolongs the survival time of the subject beyond that expected in the absence of such treatment.
2 . The method of claim 1 wherein, the quantification of percent of CD8+ T cells co-expressing PD-1 and Tim-3 is determined by Immunohistochemistry (IHC).
3 . The method of claim 1 wherein, the quantification of percent of CD8+ T cells co-expressing PD-1 and Tim-3 is determined by an automatized microscope.
4 . A method for determining whether a subject suffering from a renal cell carcinoma will achieve a response with an immune-checkpoint inhibitor and treatment of the subject comprising the steps of
i) quantifying the percent of CD8+ T cells co-expressing PD-1 and Tim-3 in a tumor tissue sample obtained from the subject treated with an immune-checkpoint inhibitor,
ii) comparing the percent CD8+ T cells co-expressing PD-1 and Tim-3 quantified at step i) with its corresponding predetermined reference values and iii) concluding that the subject will not respond to the treatment when the percent of CD8+ T cells co-expressing PD-1 and Tim-3 is higher than its corresponding predetermined reference value or concluding that the subject will respond to the treatment when the percent of CD8+ T cells co-expressing PD-1 and Tim-3 is lower than its corresponding predetermined reference value, and,
iii) administrating a therapeutically effective amount of a combination of immune checkpoint inhibitors if the subject is identified as a non-responder.
5 . The method of claim 4 , wherein the immune checkpoint inhibitor is an antibody.
6 . The method of claim 4 , wherein the immune checkpoint inhibitor is a monoclonal antibody.
7 . The method of claim 4 , wherein the immune checkpoint inhibitor is an anti-PD-1 antibody.
8 . The method of claim 4 , wherein the immune checkpoint inhibitor is an anti-PD-L1 antibody.
9 . The method of claim 4 , wherein the immune checkpoint inhibitor is an anti-PD-L2 antibody.
10 . The method of claim 4 , wherein the immune checkpoint inhibitor is an anti-Tim-3 antibody.
11 . The method of claim 4 , wherein the immune checkpoint inhibitor is a small organic molecule.
12 . The method of claim 4 , wherein the immune checkpoint inhibitor is an aptamer.
13 . (canceled)