Mus musculus Raw sequence reads
public description: Chemotherapy-induced drug resistance is a very complex process. About 80% of cancer patients received platinum treatment developed drug resistance. To investigate complicated heterotypic interactions among cancer cells and immune cells during the resistant tumor outgrowth processes under Pt treatment, we dissected the crosstalk signals with single cell RNA sequencing and performed functional study to explore Pt induced drug resistance.In this study, we have identified Lars2-S100a6 oncogenic signalling induced by Pt enhances the survival of cancer stem cells with elevated hyaluronan mediated motility receptor and mTor oncogenic pathway activity, promotes TGF-beta production in both tumor and immune cells, and induces expressions of PD1, Tim3, Selplg in T cells through cell-cell crosstalk in both tumor-bearing and wild-type mice. Combinatory treatment involving the inhibition of TGF-beta signaling, mTor pathway, and CSC maintenance, along with PD1 antibody, significantly inhibit tumor growth. This study advances the understanding of mechanism underlying Pt drug-induced resistant tumor outgrowth and proposed beneficial therapeutic strategies.