Our study observed that antibiotic allergy and EOS% >1.65 were associated with better survival of glioma. In the stratified analyses by tumor grade, the relationship between antibiotic allergy and glioma prognosis was restricted to HGG, and the association between EOS% and glioma prognosis was restricted to LGG. To the best of our knowledge, this is the first study identifying that preoperative antibiotic allergy and blood eosinophil percent were effective prognostic indicators of glioma.
Although in recent years, numerous studies have reported the inverse association between allergy and glioma risk [3, 4, 24], few studies revealed the association between allergy and the prognosis of glioma. One study focusing on history of allergy observed that history of allergy conferred a survival advantage on glioma patients in The Cancer Genome Atlas (TCGA) database [6]. Our consistent results of significant association between antibiotic allergy and glioma prognosis further confirmed the protective effect of allergy on glioma prognosis, especially HGG prognosis. Conversely, another study failed to observe a significant association between penicillin allergy and the prognosis of glioblastoma [23]. The discrepancies may be explained by the different mechanisms of antibiotics. We focused on antibiotics, mainly cephalosporins allergy, which is different from penicillin allergy. Besides, considering the number of samples, our study focused on all high-grade gliomas rather than glioblastoma.
At present, the underlying biological mechanism of the association between antibiotic allergy and favorable glioma prognosis is not entirely clear, the protective effect may be explained by the following: First, allergic patients have a more sensitive and active immune system, enhanced surveillance would protect glioma patients with antibiotic allergy have better prognosis [8]. Second, appropriately targeted allergic reactions are beneficial [25]. Allergic inflammation has been recently rediscovered to protect patients from a wide array of environmental triggers which can induce DNA damage and ultimately lead to cancer development, such as xenobiotics and carcinogens [26]. Third, antibiotic allergy was mediated by IgE [27]. Theoretically, antigen-specific IgE might promote direct tumor killing through antibody-dependent cell-mediated cytotoxicity [28], longer median survival period in glioma were associated with elevated serum IgE level[29] which was similar to the result in a mouse model of ovarian cancer [29, 30]. Finally, excessive use of antibiotics may cause pathogenic bacteria to develop resistance and toxic reactions including neurotoxic reactions [31], whereas glioma patients with antibiotic allergy could avoid excessive use of antibiotics and the resulting damage.
Eosinophils are response cells of allergic conditions, peripheral blood eosinophil percent is one of the indicators in blood routine test and necessary data for surgery patients. Therefore, we further analyzed the relationship between blood EOS% and glioma prognosis to find safe and low-cost prognostic indicators for glioma patients. Our study observed that high EOS% presented better survival of gliomas while the association restricted to LGG. However, a review reported that eosinophil may hold a functional role in the initiation, promotion and progression of the developing glioblastoma. The difference may be due to the cutoff value of EOS% being calculated based on our own data, further studies are required to reveal the relationship between EOS% and high-grade gliomas. Moreover, a preliminary study has shown that eosinophil was associated with tumor grade of glioma[32], and assumed that eosinophil could be a prognostic indicator of glioma, which was verified by our study. As innate immune cells, eosinophils participate in the construction of tumor microenvironment [33]. The experimental models and human population study suggested that the induction of an eosinophil-mediated immune response might be beneficial to counteract tumor development [26]. Furthermore, immunotherapeutic approaches have shown that eosinophilic infiltration of tumor correlates with a positive outcomes of immunotherapy [29]. The effect of eosinophils on the prognosis of glioma may be associated with the function of eosinophils. Eosinophils are able to produce growth factors, cytokines, chemokines, blood coagulants, and cytotoxic mediators that may affect each stage of tumor development [14].
To present our findings more intuitively, we constructed a nomogram that included antibiotic allergy, EOS%, tumor grade, gender and age for glioma patients. The nomogram model could effectively predict the survival probability of glioma. Furthermore, the nomogram revealed that the prognostic value of antibiotic allergy was better than EOS% for glioma patients.
As a prospective study, our study provides convincing evidence about the association between antibiotic allergy, EOS% and the prognosis of glioma, but the limitation of our study should also be considered. First, patients were from the same hospital, which may lead to selection bias. Second, all the patients didn’t receive immunotherapy treatment, we could not imply the association between antibiotic allergy, EOS% and immunotherapy treatment effect. Third, the cutoff value of EOS% was calculated based on this data, more studies are needed to evaluate the effectiveness of the cutoff value. Finally, more data is warranted to externally validate our nomogram.