Radiation therapy (RT) is used in the management of several cancers; however, tumor radioresistance remains a challenge. Polymorphonuclear neutrophils (PMNs) are recruited to the tumor immune microenvironment (TIME) post-RT and can facilitate tumor progression by forming neutrophil extracellular traps (NETs). Here, we demonstrate a role for NETs as players in tumor radioresistance. Using a syngeneic bladder cancer model, increased NET deposition is observed in the TIME of mice treated with RT and inhibition of NETs improves overall radiation response. In vitro, the protein HMGB1 promotes NET formation through a TLR4-dependent manner and in vivo, inhibition of both HMGB1 and NETs significantly delays tumor growth. Finally, NETs are observed in bladder tumors of patients who did not respond to RT and had persistent disease post-RT, wherein a high tumoral PMN-to-CD8 ratio is associated with worse overall survival. Together, these findings identify NETs as a potential therapeutic target to increase radiation efficacy.

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Purpose: To evaluate the erectile function in patients who underwent partial penectomy and identify factors associated with penile functional status. Materials and Methods: We identified patients who underwent partial penectomy due to penile cancer between 2009 and 2014. Clinical and pathological characteristics included patient age at the time of diagnosis, obesity, hypertension, dyslipidemia, diabetes, smoking, metabolic syndrome, Eastern Cooperative Oncology Group (ECOG) status, penile shaft length, tumor size, primary tumor stage (pT), clinical nodal status, and local recurrence. Erectile function was assessed prospectively with the International Index of Erectile Function (IIEF-5) at least 3 months after partial penectomy. Results: A total of 81 patients met analysis criteria. At the diagnosis, the median age was 62 years (range from 30 to 88). Median follow-up was 17 months (IQR 7-36). Of total patients, 37 (45%) had T2 or higher disease. Clinically positive nodes were present in 16 (20%) patients and seven (8.6%) developed local recurrence. Fifty patients (62%) had erectile dysfunction (ED) after partial penectomy, 30% had moderate or severe erectile dysfunction scores. Patients with ED versus without ED were similar in baseline characteristics except for age, penile shaft length, and presence of inguinal adenopathy (p <0.05). Multivariate analysis using logistic regression confirmed that older patients, shorter penile shaft length, and clinically positive lymph node were significantly associated with ED. Conclusion: Partial penectomy due to penile cancer provides adequate local control of the disease, however, proper counselling is important especially in relation to ED consequences. Preservation of penile length yields to more optimal erectile recovery.