Additionally, loss-of-function mutations involving Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), and beta-2-microglobulin (B2M) can result in cancer resistance to PD-1 blockade. The stimulation of NK cells and CD8 T-cell activity may overcome JAK1/JAK2 knockout resistance. The gene discussed is B2M; the disease is cancer.