Method of predicting for benefit from immune checkpoint inhibition therapy

1 . A method of identifying a patient suffering from cancer as benefiting or not benefiting from immune checkpoint inhibition (ICI) therapy comprising the steps of:

a) measuring an expression level of one or more preselected markers in a cancerous biological sample obtained from the patient, wherein the preselected marker is a marker that is associated with a somatic promoter region in a cancerous biological sample;

b) identifying a differentially expressed alternative promoter based on the expression level of the one or more preselected markers measured in step (a) relative to a non-cancerous biological sample, wherein an increase in the expression level of the one or more preselected markers in the cancerous biological sample compared to the expression level of the non-cancerous sample for a gained promoter indicates a differentially expressed alternative promoter, and wherein a decrease in the expression level of the one or more preselected markers in the cancerous biological sample compared to the expression level of the non-cancerous sample for a lost promoter indicates a differentially expressed alternative promoter;

c) calculating an alternative promoter usage score by determining the sum of the number of gained promoters with at least a 4-fold increase in the expression level of transcripts and the number of lost promoters with an expression level lower than 0.25-fold when compared to the median expression level of transcripts;

d) identifying the patient as benefiting or not benefiting from ICI therapy using the alternative promoter usage score by comparing the alternative promoter usage score calculated in step (c) with a reference score to identify the patient as benefiting or not benefiting from ICI therapy, wherein an increased alternative promoter usage score compared to the reference score identifies the patient as not benefiting from ICI therapy and wherein a decreased alternative promoter usage score compared to the reference score identifies the patient as benefiting from ICI therapy, wherein the reference score is the 66th or 80th percentile of alternative promoter usage scores from one or more non-cancerous biological samples; and

e) treating the patient identified as benefiting from ICI therapy with an ICI therapy.

2 . The method of claim 1 , wherein the preselected marker is a nucleic acid molecule or a peptide.

3 . The method of claim 1 , wherein the gained promoter is a promoter that is gained or increased in a cancerous biological sample compared to a non-cancerous biological sample and wherein the lost promoter is a promoter that is lost or decreased in a cancerous biological sample compared to a non-cancerous biological sample.

4 . The method of claim 1 , wherein the expression level of the one or more preselected markers in the cancerous biological sample is compared with a percentile expression level of said one or more preselected markers in the one or more non-cancerous biological samples, or the mean expression level of said one or more preselected markers in the one or more non-cancerous biological samples, or both.

5 . The method of claim 1 , wherein the increased alternative promoter usage score is a score above the 66 th or 80 th percentile of alternative promoter usage scores from one or more reference samples, and wherein the decreased alternative promoter usage score is a score below the 66 th or 80 th percentile of alternative promoter usage scores from one or more reference samples.