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

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.

Association of baseline neutrophil-to-eosinophil ratio with response to nivolumab plus ipilimumab in patients with metastatic renal cell carcinoma

“…More recently, Cheng et al reported that eosinophil-related markers are substantially increased in the TME following radiation exposure. Using mouse models, they showed that eosinophil infiltration into the TME was also markedly increased after radiation [ 28 ]. Furthermore, they showed that increased eosinophils were not only associated with recruitment of CD8+ T-lymphocytes into the TME, but also that eosinophils were necessary for the cytotoxic anti-tumor response observed.…”

Immunity and Breast Cancer: Focus on Eosinophils

“…Eosinophil depletion attenuates CD8+ T cell infiltration and decreases the efficacy of radiotherapy. In addition, stimulation of eosinophils by the administration of IL-5 increases CAR-T cell infiltration and supports the abscopal effect [ 43 ].…”

Myeloid-Derived Suppressor Cells: A Multifaceted Accomplice in Tumor Progression

“…In fact, reductions in MDSC frequency and function have been demonstrated during regular anti-tumor therapies, including chemotherapy, targeted therapy, immunotherapy, and combined therapy. However, other studies and our previous studies have shown that radiotherapy could induce an increase in MDSCs in the TME and spleen ( van Meir et al, 2017 ; Cheng et al, 2021 ). Regarding chemotherapeutic agents, 5-fluorouracil (5-FU), gemcitabine, and pemetrexed could decrease MDSC accumulation in various cancers.…”