Adenosine-producing regulatory B cells in head and neck cancer. Jeske Sandra S,Brand Matthias,Ziebart Andreas,Laban Simon,Doescher Johannes,Greve Jens,Jackson Edwin K,Hoffmann Thomas K,Brunner Cornelia,Schuler Patrick J Cancer immunology, immunotherapy : CII BACKGROUND:Multiple mechanisms of immunosuppression have been identified in the tumor microenvironment including regulatory B cells (B). Recently, we have shown that B suppress T cell function by production of adenosine (ADO). However, the autocrine effect of ADO on B cells and the role of B in head and neck cancer remains unclear. METHODS:Blood (n = 42) and tumor tissue (n = 39) of head and neck cancer patients and healthy donors (n = 60) were analyzed by FACS. The effect of ADO on phenotype, intracellular signaling pathways, Ca influx and ADO production was analyzed in B and effector B cells (B) by FACS, luminescence and mass spectrometry. The blockage of the ADO receptor A was analyzed in a murine head and neck cancer model. RESULTS:ADO-producing B were found in tumor tissue and peripheral blood. ADO inhibited the intracellular Bruton's tyrosine kinase (BTK) and Ca influx only in B. The inhibition of BTK by ibrutinib mimicked the effect of ADO, and ibrutinib reduced the production of ADO by downregulation of CD39 in vitro. The inhibition of ADO receptor A significantly reduced tumor mass and increased B cell infiltration, in vivo. CONCLUSION:Our data demonstrate the presence of a novel ADO-producing B population within the tumor microenvironment in mice and humans. A new model is proposed on how ADO-producing B can influence the function of B cells in healthy donors and cancer patients. Thus, the modulation of the ADO pathway in B cells may serve as a therapeutic approach for cancer patients. 10.1007/s00262-020-02535-6

Causes of death in patients with locally advanced head and neck cancer treated with radiotherapy and systemic therapy. Zapata I,Alvarez M,Hidalgo R,Pajares B,Garcia-Anaya M J,Toledo M D,Trigo J M,Lupiañez-Perez Y,Medina J A,Jaime Gomez-Millan J BMC cancer BACKGROUND:To investigate the incidence of non-cancer mortalities and prognostic factors associated with competitive causes of death in a homogeneous cohort of patients with locally advanced head and neck cancer treated with radiotherapy and systemic treatment. METHODS:This study included 284 patients with locally advanced head and neck cancer treated with radiotherapy and systemic treatment between 2005 and 2017. The cumulative incidence of death associated with tumour, second tumours, treatment, side effects and comorbidity was calculated. A Fine and Gray regression model was used to investigate factors associated with cancer and competitive mortality. RESULTS:The cumulative incidence of tumoral death at 5 and 10 years were 35 and 47% respectively, whereas the cumulative incidence of competitive mortality were 10 and 12% respectively. In the multivariate analysis, age and comorbidity were independent factors for non-cancer mortality. Patients with a high risk of non-cancer mortality presented a cumulative incidence of 17.3% at 5 years and 18.4% at 10 years. CONCLUSIONS:This study demonstrated a high incidence of competing mortality in older patients with comorbidities. Non-cancer deaths should be considered when selecting patients for combination therapies and in the study design ofclinical trials. 10.1186/s12885-019-6427-1

Time for a Paradigm Shift in Head and Neck Cancer Management During the COVID-19 Pandemic. Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery OBJECTIVE:The coronavirus disease 2019 (COVID-19) pandemic has caused physicians and surgeons to consider restructuring traditional cancer management paradigms. We aim to review the current evidence regarding the diagnosis and management of head and neck cancer, with an emphasis on the role of the multidisciplinary team (MDT) during a pandemic. DATA SOURCES:COVID-19 resources from PubMed, Google Scholar, the American Academy of Otolaryngology-Head and Neck Surgery, and the American Head and Neck Society were examined. REVIEW METHODS:Studies and guidelines related to the multidisciplinary management of head and neck cancer in the COVID-19 setting were reviewed. A total of 54 studies were included. Given the continuously evolving body of literature, the sources cited include the latest statements from medical and dental societies. RESULTS:The unpredictable fluctuation of hospital resources and the risk of the nosocomial spread of SARS-CoV-2 have direct effects on head and neck cancer management. Using an MDT approach to help define "essential surgery" for immediately life- or function-threatening disease processes in the context of available hospital resources will help to maximize outcomes. Early enrollment in an MDT is often critical for considering nonsurgical options to protect patients and health care workers. The role of the MDT continues after cancer treatment, if delivered, and the MDT plays an essential role in surveillance and survivorship programs in these challenging times. CONCLUSION:Head and neck cancer management during the COVID-19 pandemic poses a unique challenge for all specialists involved. Early MDT involvement is important to maximize patient outcomes and satisfaction in the context of public and community safety. 10.1177/0194599820931789

Immune Evasion by Head and Neck Cancer: Foundations for Combination Therapy. Horton Joshua D,Knochelmann Hannah M,Day Terry A,Paulos Chrystal M,Neskey David M Trends in cancer Head and neck cancer is disfiguring and deadly, and contemporary treatment has fallen short in terms of morbidity and mortality. The rich immune infiltrate within these tumors designates them as prime candidates for immunotherapy and success with these drugs has been documented for recurrent and metastatic head and neck cancer. Still, single-agent immunotherapy has generated either only transient responses or durable response in only a minority subset of patients. Mapping the immune escape mechanisms enacted by head and neck cancer within the tumor microenvironment allows for rational design of strategies to overcome this tolerance. We outline the immune pathway derangements within the head and neck cancer microenvironment and discuss combination treatment strategies to overcome the limitations of immunologic monotherapy. 10.1016/j.trecan.2019.02.007