LAUSR

35Background: A high mutation burden a biomarker of response to immune checkpoint therapy in melanoma, non-small cell lung cancer, and colorectal cancer. It is unknown whether mutation burden is predictive of response in other cancer types, and whether it is identifiable using available clinical assays. Methods: Using data for 10,745 tumors from 33 solid cancer types in TCGA, we looked for a mutation burden threshold (iCAM) in each cancer type associated with gene expression signatures of a blocked immune response of robust CD8+T cell response and up-regulation of immune checkpoint genes. Results: A unique iCAM threshold was identified in nine cancers: melanoma and lung, colon, endometrial, and gastric adenocarcinoma; serous ovarian, bladder urothelial, cervical, and ER+ HER2− breast cancer. iCAM thresholds applied to published clinical data for patients treated with immune checkpoint therapy showed that iCAM+ patients had significantly better response. iCAM+ tumors can be identified from clinical-grade N...