Data from Granulocyte colony stimulating factor is a novel mediator of T cell suppression and an immunotherapeutic target for women with colon cancer

AbstractPurpose: Granulocyte colony stimulating factor (GCSF) enhances colon cancer development. This study defines the prevalence and effects of increased GCSF signaling in human colon cancers and investigates GCSF inhibition as an immunotherapeutic strategy against metastatic colon cancer. Experimental Design: Patient samples were used to evaluate GCSF and GCSF receptor (GCSFR) levels by immunohistochemistry with sera used to measure GCSF levels. PBMCs were used to assess the rate of GCSFR+ T cells and interferon γ (IFNγ) responses to chronic ex vivo GCSF. An immune competent mouse model of peritoneal metastasis (MC38 cells in C57Bl/6J) was used to determine the effects of GCSF inhibition (αGCSF) on survival and the tumor microenvironment (TME) with flow and mass cytometry. Results: GCSF and GCSFR are increased in human colon cancer samples as compared to patient-matched normal colon. High patient serum GCSF is associated with increases in markers of poor prognosis, (e.g., VEGF, IL6). Circulating T cells from patients express GCSFR at double the rate of T cells from controls. Prolonged GCSF exposure decreases T cell IFNγ production. Treatment with αGCSF shifts both the adaptive and innate compartments of the TME and increases survival (HR=0.46, p=0.0237) and tumor T cell infiltration, activity, and IFNγ response with greater effects in female mice. A negative correlation exists between serum GCSF levels and tumor infiltrating T cells in patient samples from women. Conclusions: These findings support GCSF as an immunotherapeutic target against colon cancer with greater potential benefit in women.