Anti–VEGFR2-Interferon α Promotes the Infiltration of CD8+ T Cells in Colorectal Cancer by Upregulating the Expression of CCL5

作者：Linhua Huang, Rui Gao, Lidi Nan, Jingyao Qi, Siyu Yang, Shuai Shao, Jiajun Xie, Mingzhu Pan, Tianquan Qiu, Juan Zhang · 发表于：Journal of Immunotherapy · 年份：2024 · DOI：10.1097/cji.0000000000000516 · 被引用次数：5 · 研究领域：Cancer Immunotherapy and Biomarkers、Immune Cell Function and Interaction、CAR-T cell therapy research

SUMMARY: Immunocytokines are a promising immunotherapeutic approach in cancer therapy. Anti-VEGFR2-interferon α (IFNα) suppressed colorectal cancer (CRC) growth and enhanced CD8 + T-cell infiltration in the tumor microenvironment, exhibiting great clinical translational potential. However, the mechanism of how the anti-VEGFR2-IFNα recruits T cells has not been elucidated. Here, we demonstrated that anti-VEGFR2-IFNα suppressed CRC metastasis and enhanced CD8 + T-cell infiltration. RNA sequencing revealed a transcriptional activation of CCL5 in metastatic CRC cells, which was correlated with T-cell infiltration. IFNα but not anti-VEGFR2 could further upregulate CCL5 in tumors. In immunocompetent mice, both IFNα and anti-VEGFR2-IFNα increased the subset of tumor-infiltrating CD8 + T cells through upregulation of CCL5. Knocking down CCL5 in tumor cells attenuated the infiltration of CD8 + T cells and dampened the antitumor efficacy of anti-VEGFR2-IFNα treatment. We, therefore, propose upregulation of CCL5 is a key to enhance infiltration of CD8 + T cells in metastatic CRC with IFNα and IFNα-based immunocytokine treatments. These findings may help the development of IFNα related immune cytokines for the treatment of less infiltrated tumors.