A computer-implemented method of predicting therapeutic outcome for immune therapy of a cancer, comprising: identifying at least one of an APOBEC mutational signature and a POLE mutational signature in omics data obtained from a tumor of a patient, wherein the APOBEC signature is selected from the group consisting of: TpCpS→TpKpS, TpCpN→TpApN, and TpCpW→TpKpW, wherein S is C or G, K is G or T, N is C or G or A or T, and W is A or T, and/or wherein the POLE signature is selected from the group consisting of: TpCpT→TpApT and TpTpT→TpGpT; quantifying expression of a plurality of genes associated with checkpoint inhibition from the omics data, wherein the genes associated with checkpoint inhibition are selected from the group consisting of: IDO, TDO, TIM3, CD40, LAG3, PD-L1, PD-L2, CTLA4, PD1, and IL2; determining an MSI status from the omics data; and using the APOBEC mutational signature and/or POLE mutational signature, the determined expression quantity of the plurality of genes, and the MSI status to update or generate a patient profile that indicates a prediction of therapeutic outcome for the immune therapy of the cancer, wherein: i) the presence of the APOBEC mutational signature and/or the POLE mutational signature is indicative of a favorable therapeutic outcome; ii) a positive MSI is indicative of a favorable therapeutic outcome; and iii) over-expression of the plurality of genes associated with checkpoint inhibition is indicative of a favorable therapeutic outcome. identifying at least one of an APOBEC mutational signature and a POLE mutational signature in omics data obtained from a tumor of a patient, wherein the APOBEC signature is selected from the group consisting of: TpCpS→TpKpS, TpCpN→TpApN, and TpCpW→TpKpW, wherein S is C or G, K is G or T, N is C or G or A or T, and W is A or T, and/or wherein the POLE signature is selected from the group consisting of: TpCpT→TpApT and TpTpT→TpGpT; quantifying expression of a plurality of genes associated with checkpoint inhibition from the omics data, wherein the genes associated with checkpoint inhibition are selected from the group consisting of: IDO, TDO, TIM3, CD40, LAG3, PD-L1, PD-L2, CTLA4, PD1, and IL2; determining an MSI status from the omics data; and using the APOBEC mutational signature and/or POLE mutational signature, the determined expression quantity of the plurality of genes, and the MSI status to update or generate a patient profile that indicates a prediction of therapeutic outcome for the immune therapy of the cancer, wherein: i) the presence of the APOBEC mutational signature and/or the POLE mutational signature is indicative of a favorable therapeutic outcome; ii) a positive MSI is indicative of a favorable therapeutic outcome; and iii) over-expression of the plurality of genes associated with checkpoint inhibition is indicative of a favorable therapeutic outcome. i) the presence of the APOBEC mutational signature and/or the POLE mutational signature is indicative of a favorable therapeutic outcome; ii) a positive MSI is indicative of a favorable therapeutic outcome; and iii) over-expression of the plurality of genes associated with checkpoint inhibition is indicative of a favorable therapeutic outcome.