2.8. Gene Prioritization of C3, C5, C3AR1, and C5AR1 across Four Immunosuppressive Indices

In order to identify potential gene targets, we used the regulator prioritization module of the TIDE algorithm to rank the importance of the genes based on the dysfunction and risk scores computed from clinical studies and CRISPR screening processes. We assessed the gene prioritization of C3, C5, C3AR1, and C5AR1 across four immunosuppressive parameters, including T-cell exclusion score, T-cell dysfunction score, response to immune checkpoint blockade (ICB) therapy, and gene knockout phenotype in CRISPR screens. The T-cell dysfunction score was used to evaluate how C3, C5, C5AR1, and C3AR1 interact with cytotoxic T cells to influence the survival of cancer patients, while the T-cell exclusion score was used to evaluate the collective effect of three immunosuppressive cell types (CAF, MDSCs, and M2-TAMs) on T-cell exclusion in the TME. The z-score in the Cox PH regression was used to evaluate the effect of the gene expression on patient survival in ICB treatment cohorts. The normalized logFC in CRISPR screens was employed in the evaluation of the effect of gene-knockout-mediated and lymphocyte-induced tumor death in cancer models [35].