MSS tumors show effective DNA mismatch repair and are more resistant to ICI therapy.[50] Meanwhile, MSI tumors, which often experience DNA mutations due to their defects in DNA mismatch repair proteins, are more sensitive to ICI therapy.[51] Our findings showed that while ICI therapy using anti‐PD‐L1 antibody failed to exert any significant effect on MSS tumors, pyroptosis triggered by YY2‐induced chromosome missegregation could increase inflammatory environment in MSS tumors, thereby activating the CTL cells, and subsequently decreasing their resistance to immunotherapy. The gene discussed is YY2; the disease is Marinesco-Sjogren syndrome.