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Background <p>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.</p> Methods <p>We used single-cell RNA sequencing, flow cytometry, and functional assays in <i>Linc00673</i> knockout and wild-type mouse models treated with programmed death 1 (PD-1) blockade to dissect changes in immune landscape and tumor cell behavior.</p> Results <p><i>Linc00673</i> 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. <i>Linc00673</i> also promoted tumor cell migration and immune evasion independently of immune cells, suggesting dual tumor-intrinsic and -extrinsic roles.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月3日

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

摘要

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.