Signatures for predicting cancer immune therapy response

A system for detecting resistance, or an increased likelihood of resistance, to a treatment regimen comprising an immune checkpoint inhibitor, the system comprising:

• (1) a sample analyzer for assaying one or more patient samples comprising or derived from a cancer cell to determine or detect the sequence of at least a portion of each test gene in a panel of genes comprising the following antigen processing machinery genes:
• Beta-2-Microglobulin (B2M), Class II Major Histocompatibility Complex Transactivator (CIITA), Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), Endoplasmic Reticulum Aminopeptidase 2 (ERAP2), NLR family CARD domain containing 5 (NLRC5), Transporter 1, ATP Binding Cassette Subfamily B Member (TAP1), Transporter 1, ATP Binding Cassette Subfamily B Member (TAP2), and TAP binding protein (TAPBP);
• (2) a first computer program for receiving test genetic sequence data on the test genes;
• (3) a second computer program for comparing the test genetic sequence data to one or more reference genetic sequences for each test gene to determine whether any of the test genes harbors a mutation;
• and
• (4) a third computer program for determining:
• (a) that a patient in whose sample at least one test gene is determined by the second computer program in (3) to harbor a mutation has an increased likelihood of resistance to a treatment regimen comprising an immune checkpoint inhibitor;
• or
• (b) that a patient in whose sample no test gene is determined by the second computer program in (3) to harbor a mutation has a decreased likelihood of resistance to a treatment regimen comprising an immune checkpoint inhibitor,
• wherein the system further comprises a display module displaying the comparison between the test genetic sequence date and the reference sequence(s), or displaying a result of the computerized comparison.

A method for treating a cancer patient, comprising:

• a) sequencing genomic DNA isolated from a sample comprising cancer cell from a subject that is a candidate for a treatment regimen comprising an immune checkpoint inhibitor for a sequence of at least a portion of each test gene in a panel of genes comprising the following antigen processing machinery genes:
• Beta-2-Microglobulin (B2M), Class II Major Histocompatibility Complex Transactivator (CIITA), Endoplasmic Reticulum Aminopeptidase 1 (ERAP1), Endoplasmic Reticulum Aminopeptidase 2 (ERAP2), NLR family CARD domain containing 5 (NLRC5), Transporter 1, ATP Binding Cassette Subfamily B Member (TAP1), Transporter 1, ATP Binding Cassette Subfamily B Member (TAP2), and TAP binding protein (TAPBP);
• b) detecting a mutation in any of the test genes that results in low expression of the test gene or any protein encoded thereby, and
• c) administering a treatment regimen comprising an immune checkpoint inhibitor to the patient in whose sample no test gene is determined in (b) to have low expression.