Investigation of the key factors that induce the immune heterogeneity between LUAD and LUSC would provide a glimpse of the different responses of lung cancer subtypes to immunotherapy.17 First, compared with adjacent tissues, although the co-existence of some immune function-related genes, were co-expressed in the two main cancer subtypes, the HLA-D family, NKG7, GNLY, and immune-related gene FCGR3A were enriched in LUAD, whereas LUSC distinctly expressed prognosis-related genes, such as IGHG3, IGHG4, IGHG1 and IGKC (Supplementary Fig. 2a). Here, IGHG4 is linked to lung cancer.