Anti-LTBR monoclonal antibody, clone fCjp4D9

The cytokines lymphotoxin (LT) alpha, beta and their receptor (LT beta R) belong to the tumor necrosis factor (TNF) superfamily, whose founder-TNF alpha-was initially discovered due to its tumor necrotizing activity. LT beta R signaling serves pleiotropic functions including the control of lymphoid organ development, support of efficient immune responses against pathogens due to maintenance of intact lymphoid structures, induction of tertiary lymphoid organs, liver regeneration or control of lipid homeostasis. Signaling through LTbR comprises the noncanonical/canonical nuclear factor-kappa B (NF-kappa B) pathways thus inducing chemokine, cytokine or adhesion molecule expression, cell proliferation and cell survival. Blocking LT beta R signaling or Fc gamma-receptor mediated immunoablation of LT-expressing cells was demonstrated to be beneficial in various infectious or noninfectious inflammatory or autoimmune disorders. Only recently, LT beta R signaling was shown to initiate inflammation-induced carcinogenesis, to influence primary tumorigenesis and to control reemergence of carcinoma in various cancer models through distinct mechanisms. Indeed, LT beta R signaling inhibition has already been used as efficient anti-inflammatory, anti-cancer therapy in some experimental models. Here, we review the pleiotropic functions attributed to LT, the effects of its deregulation and extensively discuss the recent literature on LT's link to carcinogenesis. Oncogene (2010) 29, 5006-5018; doi:10.1038/onc.2010.260; published online 5 July 2010

Objective: To evaluate postoperative hearing outcomes after lateral temporal bone resection (LTBR) with reconstruction of the external auditory canal (EAC) and conductive function for early-stage EAC carcinoma. Methods: We retrospectively examined patients diagnosed with early-stage EAC carcinoma treated with surgery alone between January 2006 and December 2012. Patients who had postoperative adjuvant chemotherapy and/or radiotherapy were excluded. Patients receiving LTBR in combination with tympanoplasty were divided into two groups based on the reconstruction of the EAC with and without (w/o) split-thickness skin grafts (STSGs). Audiological data included the preoperative hearing thresholds and the most recent postoperative hearing thresholds obtained at least 12 months after surgery. The hearing outcome was evaluated based on puretone audiograms using the Committee on Hearing and Equilibrium guidelines of the American Academy of Otolaryngology-Head and Neck Surgery for the evaluation of the results of treatment of conductive hearing loss. The postoperative quality of life (QOL) for patients was evaluated using the Glasgow Benefit Inventory (GBI). Results: All patients (n = 15) achieved disease-free survival without significant morbidity or mortality. When we compared the mean air-bone gaps after surgery, those in the STSG group (n = 8) were found to be significantly lower than those in the w/o STSG group (n = 7; p < 0.001). The success rate for postoperative hearing was 75.0% in the STSG group, which was significantly higher than that in the w/o STSG group (p = 0.014). All patients in the w/o STSG group showed stenosis and closure of the EAC at fewer than 10 months after surgery. In contrast, all patients in the STSG group showed preserved conformation of the new EAC for more than 12 months after surgery. When we compared the mean GBI score between the two groups of patients, the overall and general health scores in the STSG group were found to be significantly higher than those in the w/o STSG group (p = 0.021, p = 0.001). Conclusions: Reconstruction of the EAC using a rolled-up STSG technique in combination with tympanoplasty after LTBR is useful for hearing preservation and the observation of locoregional lesions after surgery, resulting in improved QOL for patients. (C) 2014 S. Karger AG, Basel