Radiation-induced eosinophils improve cytotoxic T lymphocyte recruitment and response to immunotherapy

放射诱导的嗜酸性粒细胞可改善细胞毒性 T 淋巴细胞的募集和对免疫疗法的反应

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作者:Jia-Nan Cheng, Wen Luo, Chengdu Sun, Zheng Jin, Xianghua Zeng, Peter B Alexander, Zhihua Gong, Xin Xia, Xiaofang Ding, Shouxia Xu, Ping Zou, Yisong Y Wan, Qingzhu Jia, Qi-Jing Li, Bo Zhu

Abstract

The efficacy of cancer immunotherapy is dictated by CD8+ T cell infiltration and the nature of the tumor microenvironment (TME). By inflaming the TME to favor CD8+ T cell immunity, radiation is now widely considered as a neoadjuvant for immunomodulation. Here, we observed that local irradiation enhances the infiltration of intratumoral eosinophils, and depletion of eosinophil dampens CD8+ T cell infiltration and diminishes the anti-tumor effectiveness of radiation. Retrospectively, we identified a strong correlation between eosinophilia and survival benefit in radiation-treated cancer patients. Experimentally, we further show that radiation enhances the intratumoral infiltration of adoptive transferred T cells therapy, bolstering eosinophils by intravenous interleukin-5 administration promotes the efficacy of radiation-induced abscopal effect. Together, these results suggest that eosinophil mobilization can be considered as a mechanistically relevant biomarker for predicting the effectiveness of pre-immunotherapy radiation, as well as a new strategy to enhance T cell-mediated immunotherapy against cancers.

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