Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immature myeloid cells that expand in tumor bearing hosts in response to soluble factors produced by tumor and stromal cells. MDSC expansion has been linked to loss of immune effector cell function and reduced efficacy of immune-based cancer therapies, highlighting the MDSC population as an attractive therapeutic target. Ibrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase (BTK) and IL2-inducible T-cell kinase (ITK), is in clinical use for the treatment of B cell malignancies. Here, we report that BTK is expressed by murine and human MDSCs, and that ibrutinib is able to inhibit BTK phosphorylation in these cells. Treatment of MDSCs with ibrutinib significantly impaired nitric oxide production and cell migration. In addition, ibrutinib inhibited in vitro generation of human MDSCs and reduced mRNA expression of indolamine 2,3-dioxygenase, an immunosuppressive factor. Treatment of mice bearing EMT6 mammary tumors with ibrutinib resulted in reduced frequency of MDSCs in both the spleen and tumor. Ibrutinib treatment also resulted in a significant reduction of MDSCs in wildtype mice bearing B16F10 melanoma tumors, but not in X-linked immunodeficiency mice (XID) harboring a BTK mutation, suggesting that BTK inhibition plays an important role in the observed reduction of MDSCs in vivo. Finally, ibrutinib significantly enhanced the efficacy of anti-PD-L1 (CD274) therapy in a murine breast cancer model. Together, these results demonstrate that ibrutinib modulates MDSC function and generation, revealing a potential strategy for enhancing immune-based therapies in solid malignancies.

Objective To report long-term, health-related quality-of-life (HRQOL) outcomes in patients treated with transoral robotic surgery (TORS). Study Design Prospective, longitudinal, clinical study on functional and HRQOL outcomes in TORS. Setting University tertiary care facility. Subjects and Methods Patients who underwent TORS were asked to complete a Head and Neck Cancer Inventory before treatment and at 3 weeks and 3, 6, and 12 months postoperatively. Demographic, clinicopathological, and follow-up data were collected. Results Sixty-four patients who underwent TORS were enrolled. A total of 113 TORS procedures were performed. The mean follow-up time was 16.3 ± 7.49 months. The HRQOL was assessed at 3 weeks and at 3, 6, and 12 months, with a response rate of 78%, 44%, 41%, and 28%, respectively. TORS was performed most frequently for squamous cell carcinoma (88%). There was a decrease from baseline in the speech, eating, aesthetic, social, and overall QOL domains immediately after treatment. At the 1-year follow-up, the HRQOL scores in the aesthetic, social, and overall QOL domains were in the high domain. Patients with malignant lesions had significantly lower postoperative HRQOL scores in the speech, eating, social, and overall QOL domains (P < .05). Patients who underwent adjuvant radiation therapy or chemotherapy and radiation therapy had lower postoperative scores in the eating, social, and overall QOL domains (P < .05). Conclusion The preliminary data show that patients who undergo TORS for malignancies and receive adjuvant therapy tend to have lower HRQOL outcomes. TORS is a promising, minimally invasive, endoscopic alternative surgical treatment of laryngopharyngeal tumors.

The 30dURs in patients who undergo head and neck surgery can be low, but costly. Identifying patients at risk for 30dUR will help develop preventative strategies. © 2015 Wiley Periodicals, Inc. Head Neck 38: E502-E510, 2016.