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.
Triple-negative breast cancer (TNBC) accounts for 15-30% of all breast cancer cases and is clinically difficult to treat due to the lack of hormone or human epidermal growth factor receptor 2 receptors, which are usually targeted by the most successful therapeutic approaches. Immune checkpoint inhibitors (ICIs) have offered long-term survival benefits in several types of solid tumors, however with low response rates. Thus, there is an urgent need to develop feasible biomarkers for identifying patients with TNBC, who are responsive. The present study demonstrated that the immune microenvironment of TNBC has the highest expression of immunoregulatory molecules among all pathologic types. The tumor mutation burden (TMB) of TNBC was not strongly correlated with cytolytic activity and showed no significant associations with different degrees of immune cell infiltration and TMB. The machine learning method divided patients with TNBC into two groups characterized by 'hot' and 'cold' tumors, according to whether immune-associated genes were highly expressed, and different responses to immunotherapy were seen between these two groups. Furthermore, patients with a TP53 Mut PIK3CA Wild genotype demonstrated favorable immunotherapy-responsive signatures and may have improved outcomes with ICIs. In conclusion, the present study revealed that TP53 and PIK3CA may be appropriate biomarkers to screen for patients who would benefit most from ICIs, which could guide precise immunotherapy for patients with TNBC.
Arbuscular mycorrhizal (AM) fungi form intimate associations with the roots of about 85% of all terrestrial plants, and can greatly increase a plant's uptake of soil nutrients and have been shown to influence plant diversity in several ecosystems. A lot of studies have reported the effect of arbuscular mycorrhizas on plant density, species diversity, richness and productivity in desert herbland in Gurbantonggut desert, China. Here, we conduct a mycorrhizal functional study by suppressing AM fungi by applying the fungicide benomyl as a soil drench in soil cores and field in-situ experiment. The mycorrhiza-responsiveness of the dominant species Erodium oxyrrhynchum is assessed in intact soil cores containing the indigenous AM fungi. The soil-cores experiment displayed E. oxyrrhynchum to have a significant positive shoot and root growth response, and this is in response to the abundance of the indigenous AM fungal colonisation. The field experiment indicates the total aboveground dry biomass is negatively influenced by the suppression of AM fungi, though, no significant effect produced in the dominant and common plant species. The fungal suppression also affected density, species diversity and richness. The density of non-mycorrhizal plant Alyssum linifolium increases significantly in the treatment of suppressed AM fungi. The spore density decreases significantly in benomyl-treated plots. Our results showed that AM fungi were very important in desert ecosystem for the maintaining of plant biodiversity, richness and productivity.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.