PMID- 35551664 OWN - NLM STAT- Publisher VI - 183 TI - The Single-Cell Level Perspective of the Tumor Microenvironment and Its Remodeling by CAR-T Cells. PG - 275-285 CI - © 2022. The Author(s), under exclusive license to Springer Nature Switzerland AG. LA - eng PT - Journal Article PL - United States TA - Cancer Treat Res JT - Cancer treatment and research JID - 8008541 IS - 0927-3042 (Print) LID - 10.1007/978-3-030-96376-7_10 [doi] FAU - Gao, Sanxing AU - Gao S AD - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong. FAU - Sugimura, Ryohichi AU - Sugimura R AD - School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pok Fu Lam, Hong Kong. Rios@hku.hk. IS - 0927-3042 (Linking) SB - IM LR - 20220513 DP - 2022 AB - The tumor microenvironment (TME) is a complex milieu consisting of lymphoid cells, myeloid cells, fibroblasts, and multiple molecules, which play a key role in tumor progression and immunotherapy. TME is characterized by immune-suppressive features, which release anti-inflammatory cytokines such as IL-4 and TGFβ to skew the T cells to a Th2 state as well to polarize tumor-associated macrophages (TAMs) to an anti-inflammatory phenotype to curb the immunotherapy. Considering the heterogeneity of the TME and its role in determining response to chimeric antigen receptor (CAR)-T cells, delineating TME at a single-cell level will provide useful information for cancer treatment. First, we discuss cellular and molecular features that curb the response to CAR-T cells, for example, high expression of immune checkpoint molecules (PD-1, LAG3) and anti-inflammatory cytokines (IL-4, TGFb) that block CAR-T cell function. Then, we summarize how newly invented single-cell technologies such as spatial multi-omics would benefit the understanding of cancer immunotherapy. Finally, we will further describe recent attempts of CAR-T to remodel TME by arming the CAR-T with anti-PD-1 single-chain variants or Th1 triggering cytokines (such as IL-7, IL-12) to remodel TME into a pro-inflammatory state. Herein, we review the single-cell-level signatures of TME and the strategies of CAR-T to remodel TME.