Journal Article

Single-cell RNA sequencing unveils enhanced antitumor immunity in colorectal cancer with PD-1 blockade and LINC00673 deletion

Wei, Ping, Yao, Yanxi, Li, Dawei, Li, Yuxue, Qiu, Zhibing, Zhu, Yifei, Huang, Huixia, Sun, Qingyang, Tang, Jianqiang, Wang, Yaxian, Chen, Keji, Zhou, Dingpei, Chen, Jiayu

2026

Overview

Background Most colorectal cancers are resistant to immune checkpoint inhibitors due to an immunosuppressive tumor microenvironment. LINC00673, previously classified as a long non-coding RNA, has been implicated in tumor progression, but its role in antitumor immunity remains poorly understood. Methods We used single-cell RNA sequencing, flow cytometry, and functional assays in Linc00673 knockout and wild-type mouse models treated with programmed death 1 (PD-1) blockade to dissect changes in immune landscape and tumor cell behavior. Results Linc00673 deletion enhanced the efficacy of PD-1 therapy, reducing tumor burden and prolonging survival. KO tumors showed increased infiltration of cytotoxic CD8⁺ T cells, reduced exhaustion, and improved antigen presentation. The tumor microenvironment shifted toward a pro-inflammatory state, with elevated dendritic cell function, reduced immunosuppressive macrophages, and improved T cell–tumor interactions. Linc00673 also promoted tumor cell migration and immune evasion independently of immune cells, suggesting dual tumor-intrinsic and -extrinsic roles. Conclusions LINC00673 suppresses antitumor immunity and promotes tumor aggressiveness. Its deletion synergizes with PD-1 blockade, revealing a promising therapeutic target to overcome immune resistance in colorectal cancer.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Animal models / Antigen presentation / Antigens / Apoptosis / Biomarkers / Biomedical and Life Sciences / Biomedicine / Cancer Research / CD8 antigen / Cell growth / Clonal deletion / Colorectal cancer / Cytotoxicity / Dendritic cells / Flow cytometry / Health aspects / Immune checkpoint inhibitors / Immunity / Immunotherapy / Inflammatory bowel disease / Laboratory animals / Leukocyte migration / LINC00673 / Lung cancer / Lymphocytes T / Macrophages / Metastases / PD-1 protein / RNA / RNA sequencing / RNA-protein interactions / Single-cell RNA sequencing / T cells / Therapeutic targets / Tumor microenvironment / Tumors / Yeast