Andrew S Azman, James H Stark, Benjamin M Althouse, Charles J Vukotich, Samuel Stebbins, Donald S Burke, Derek A T Cummings
Household transmission of influenza A and B in a school-based study of non-pharmaceutical interventions
Epidemics
tumourinfiltrating lymphocytes tils crucial effective immune checkpoint blockade icb therapy solid tumours however 70 tumours exhibit poor lymphocyte infiltration rendering icb therapies less effective developed bioinformatics pipeline integrating multiple previously unconsidered factors datasets including tumour cell immunerelated pathways copy number variation cnv single tumour cell sequencing data well tumour mrnaseq data patient survival data identify targets potentially improve cell infiltration enhance icb efficacy furthermore conducted wetlab experiments successfully validated one topidentified genes applied pipeline solid tumours cancer genome atlas tcga identified set genes 18 cancer types might potentially improve lymphocyte infiltration icb efficacy providing valuable drug target resource explored importantly experimentally validated sun1 linked cell infiltration icb therapy previously one topidentified gene targets among 3 cancer types based pipeline mouse colon cancer syngeneic model showed sun1 ko could significantly enhance antigen presentation increase tcell infiltration improve antipd1 treatment efficacy moreover singlecell multiome analysis identified subgene regulatory networks subgrns showing stat proteins play important roles enhancing immunerelated pathways sun1ko cancer cells study established computational pipeline discovering new gene targets signalling pathways cancer cells block tcell infiltration also provided gene target pool exploration improving lymphocyte infiltration icb efficacy solid tumours full list funding bodies contributed study found acknowledgements section