Methods and systems for assessing proliferative potential and resistance to immune checkpoint blockade

A method for treating a tumor, comprising:

• obtaining tissue from the tumor;
• measuring, using the tissue, expression of one or more cell proliferation gene markers, wherein the one or more cell proliferation gene markers comprises one or more of BUB1, CCNB2, CDK1, CDKN3, FOXM1, KIAA0101, MAD2L1, MELK, MKI67, and TOP2A;
• determining, based on the measured expression of the one or more cell proliferation gene markers, a proliferation profile of the tumor, wherein the determined proliferation profile of the tumor comprises one or more of poorly proliferative, moderately proliferative, and highly proliferative;
• measuring, using the tissue, PD-L1 expression;
• determining, based on the measured PD-L1 expression, a PD-L1 profile for the tumor, wherein the PD-L1 profile may be PD-L1 positive or PD-L1 negative;
• predicting, based on the determined proliferation profile and the determined PD-L1 profile, response of the tumor to immune checkpoint blockade therapy;
• and
• determining, by a physician using the predicted response of the tumor to immune checkpoint blockade therapy, a therapy for the tumor, wherein the determined therapy comprises immune checkpoint blockade therapy if the predicted response is favorable, and wherein the determined therapy comprises a therapy other than immune checkpoint blockade therapy if the predicted response is not favorable;
• and
• applying the determined therapy to the tumor;
• wherein the moderately proliferative proliferation profile is associated with a predicted more favorable response of the tumor to immune checkpoint blockade therapy, and wherein the poorly proliferative proliferation profile and the highly proliferative proliferation profile are associated with a predicted less favorable response of the tumor to immune checkpoint blockade therapy.

An assay for characterizing tumor resistance to immune checkpoint blockade, comprising:

• a measured expression of one or more cell proliferation gene markers obtained from tumor tissue;
• a determined proliferation profile of the tumor based on measured expression of one or more cell proliferation gene markers in the tumor tissue;
• a predicted response of the tumor to immune checkpoint blockade therapy based on the determined proliferation profile;
• and
• a therapy for the tumor determined by physician using the predicted response of the tumor to immune checkpoint blockade therapy.