Head-to-Head Comparison of CCN4, DNMT3A, PTPN11, and SPARC as Suppressors of Anti-tumor Immunity.

Purpose: Emergent cancer cells likely secrete factors that inhibit anti-tumor immunity. To identify such factors, we applied a functional assay with proteomics to an immunotherapy resistant syngeneic mouse melanoma model. Four secreted factors were identified that potentially mediate immunosuppression and could become targets for novel immunotherapies.

Data-driven learning how oncogenic gene expression locally alters heterocellular networks.

Developing drugs increasingly relies on mechanistic modeling and simulation. Models that capture causal relations among genetic drivers of oncogenesis, functional plasticity, and host immunity complement wet experiments. Unfortunately, formulating such mechanistic cell-level models currently relies on hand curation, which can bias how data is interpreted or the priority of drug targets.

Cell Communication Network factor 4 promotes tumor-induced immunosuppression in melanoma.

Cell Communication Network factor 4 (CCN4/WISP1) is a matricellular protein secreted by cancer cells that promotes metastasis by inducing the epithelial-mesenchymal transition. While metastasis limits survival, limited anti-tumor immunity also associates with poor patient outcomes with recent work linking these two clinical correlates. Motivated by increased CCN4 correlating with dampened anti-tumor immunity in primary melanoma, we test for a direct causal link by knocking out CCN4 (CCN4 KO) in the B16F0 and YUMM1.