In the current study, we have provided large-scale germline genetic and tightly coupled immune, somatic and functional genomic evidence to support a deeper evaluation of the proteins encoded by IRF1, IKZF1, SPI1, SH2B3 and LAT as possible targets for cancer immunotherapy, particularly in breast, prostate, ovarian and endometrial cancers where there is substantial unmet need for new immunotherapeutic targets. The gene discussed is SPI1; the disease is cancer.