While anti-tumor activity in cancers lacking both HLA-II and HLA-I expression is thought to be coordinated by NK and CD4+ T cells64,65, we propose that the distinct expression of HLA-II on NSCLC cells presents a viable pathway for cytotoxic CD4+ T cells to drive ICB response in HLA-I-disrupted patients. Here, CD4 is linked to non-small cell lung carcinoma.