scCURE identifies cell types responding to immunotherapy and enables outcome prediction.

A deep understanding of immunotherapy response/resistance mechanisms and a highly reliable therapy response prediction are vital for cancer treatment. Here, we developed scCURE (single-cell RNA sequencing [scRNA-seq] data-based Changed and Unchanged cell Recognition during immunotherapy). Based on Gaussian mixture modeling, Kullback-Leibler (KL) divergence, and mutual nearest-neighbors criteria, scCURE can faithfully discriminate between cells affected or unaffected by immunotherapy intervention. By conducting scCURE analyses in melanoma and breast cancer immunotherapy scRNA-seq data, we found that the baseline profiles of specific CD8 T and macrophage cells (identified by scCURE) can determine the way in which tumor microenvironment immune cells respond to immunotherapy, e.g., antitumor immunity activation or de-activation; therefore, these cells could be predictive factors for treatment response. In this work, we demonstrated that the immunotherapy-associated cell-cell heterogeneities revealed by scCURE can be utilized to integrate the therapy response mechanism study and prediction model construction.