ArticleDiscover oncology2026
Circ_0001313 promotes an immunosuppressive tumor microenvironment through GM-CSF-associated granulocytic myeloid cell activation in colorectal cancer.
Article in Discover oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundCirc_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.
methodsCirc_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.
resultsCirc_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.
conclusionCirc_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.
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