Knockout of immunotherapy prognostic marker genes eliminates the effect of the anti-PD-1 treatment

We present a pan-cancer integrated analysis of transcriptome, exome and clinical records of patients. Herein, we identified candidate genes as potential biomarkers to predict clinical outcome of immunotherapy. We further explored the function of two IPM genes in vivo. Knockout of MALT1, which is critical for the T cell receptor signaling, can eliminate the anti-tumor effect of anti-PD-1 treatment completely by impairing the activation of CD8+ T cells. Notably, knockout of CLEC4D, a C-type lectin receptor that expressed on myeloid cells, also reduced the effect of anti-PD-1 treatment potentially through maintaining the immunosuppressive effects of myeloid cells. Macrophages and MDSCs cells sorted from wild type (WT) or Clec4d KO mice with anti-PD-1 or IgG treatment were used for RNA extraction and RNA-sequencing