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Background <p>Circ_0001313 is upregulated in colorectal cancer (CRC) and has been implicated in tumor progression, but its role in remodeling the immune microenvironment remains incompletely defined. This study investigated whether circ_0001313 contributes to CRC progression in association with granulocytic myeloid-derived suppressor cell (gMDSC)-like immunosuppression.</p> Methods <p>Circ_0001313 expression was evaluated by qRT-PCR in CRC tissues and cell lines. Functional studies were performed using transient siRNA-mediated circ_0001313 knockdown in MC38 cells, a syngeneic murine CRC model suitable for immunocompetent C57BL/6J mice, followed by subcutaneous tumor growth and experimental lung metastasis assays. Tumor immune composition was analyzed by flow cytometry, Ly6G+ granulocytic myeloid cell-mediated suppression of CD8 + T-cell proliferation was assessed by coculture, and tumor explant supernatant (TES) assays, qPCR, ELISA, and GM-CSF neutralization were used to examine a GM-CSF-associated mechanism linked to gMDSC-like activation.</p> Results <p>Circ_0001313 was upregulated in CRC tissues and cell lines. Transient circ_0001313 knockdown suppressed primary tumor growth and prolonged survival in the lung metastasis model. Immune profiling showed increased intratumoral CD4 + and CD8 + T cells but reduced Ly6G+ granulocytic myeloid cell abundance after circ_0001313 silencing. Ly6G+ cells from circ_0001313-silenced tumors exhibited lower PD-L1 and arginase 1 expression and diminished suppression of CD8 + T-cell proliferation. Mechanistically, circ_0001313 depletion was associated with reduced tumor-derived GM-CSF expression, and GM-CSF neutralization attenuated TES-induced gMDSC-like activation.</p> Conclusion <p>Circ_0001313 promotes CRC progression, at least in part, by remodeling the tumor immune microenvironment through a GM-CSF-associated granulocytic suppressor program, supporting further evaluation of this axis as a potential therapeutic target in CRC.</p>

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Circ_0001313 promotes an immunosuppressive tumor microenvironment through GM-CSF-associated granulocytic myeloid cell activation in colorectal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月27日

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  • Ya Liu,
  • Longfei Liu,
  • Yingping Quan,
  • Li Wang,
  • Jiaotao Xing,
  • Jun Zhao,
  • Hui Wang

摘要

Background

Circ_0001313 is upregulated in colorectal cancer (CRC) and has been implicated in tumor progression, but its role in remodeling the immune microenvironment remains incompletely defined. This study investigated whether circ_0001313 contributes to CRC progression in association with granulocytic myeloid-derived suppressor cell (gMDSC)-like immunosuppression.

Methods

Circ_0001313 expression was evaluated by qRT-PCR in CRC tissues and cell lines. Functional studies were performed using transient siRNA-mediated circ_0001313 knockdown in MC38 cells, a syngeneic murine CRC model suitable for immunocompetent C57BL/6J mice, followed by subcutaneous tumor growth and experimental lung metastasis assays. Tumor immune composition was analyzed by flow cytometry, Ly6G+ granulocytic myeloid cell-mediated suppression of CD8 + T-cell proliferation was assessed by coculture, and tumor explant supernatant (TES) assays, qPCR, ELISA, and GM-CSF neutralization were used to examine a GM-CSF-associated mechanism linked to gMDSC-like activation.

Results

Circ_0001313 was upregulated in CRC tissues and cell lines. Transient circ_0001313 knockdown suppressed primary tumor growth and prolonged survival in the lung metastasis model. Immune profiling showed increased intratumoral CD4 + and CD8 + T cells but reduced Ly6G+ granulocytic myeloid cell abundance after circ_0001313 silencing. Ly6G+ cells from circ_0001313-silenced tumors exhibited lower PD-L1 and arginase 1 expression and diminished suppression of CD8 + T-cell proliferation. Mechanistically, circ_0001313 depletion was associated with reduced tumor-derived GM-CSF expression, and GM-CSF neutralization attenuated TES-induced gMDSC-like activation.

Conclusion

Circ_0001313 promotes CRC progression, at least in part, by remodeling the tumor immune microenvironment through a GM-CSF-associated granulocytic suppressor program, supporting further evaluation of this axis as a potential therapeutic target in CRC.