Head and Neck Cancer Immunotherapy beyond the Checkpoint Blockade.

The success of immune checkpoint receptor blockade has brought exciting promises for the treatment of head and neck squamous cell carcinoma (HNSCC). While patients who respond to checkpoint inhibitors tend to develop a durable response, <15% of patients with HNSCC respond to immune checkpoint inhibitors, underscoring the critical need to alleviate cancer resistance to immunotherapy. Major advances have been made to elucidate the intrinsic and adaptive resistance mechanisms to immunotherapy. Central genomic events in HNSCC have been found to possess previously unknown roles in suppressing immune sensing. Such inhibitory function affects both the innate and adaptive arms of tumor-specific immunity. While checkpoint blockade effectively reinvigorates adaptive T-cell responses, additional targeting of the oncogenic inhibitors of innate immune sensing likely informs a novel and potent strategy for immune priming. This review discusses the recent advances on the identification of key HNSCC oncogenes that impair antitumor immunity and emerging immune-priming approaches that sensitize poorly immunogenic HNSCCs to checkpoint blockade. These approaches include but are not limited to cancer vaccine systems utilizing novel type I interferon agonists as immune adjuvants, radiation, DNA damage-inducing agents, and metabolic reprogramming. The goal of these multipronged approaches is to expand tumor-specific effector T-cells, break checkpoint receptor-mediated tolerance, and metabolically support sustained T-cell activation. The translation of therapeutics that reverses oncogenic inhibition of immune sensing requires thorough characterization of the HNSCC regulators of innate immune sensors, development of additional immunocompetent HNSCC mouse models, as well as engineering of more robust immune adjuvant delivery systems. Built on the success of checkpoint blockade, validation of novel immune-priming approaches holds key promises to expand the pool of responders to immunotherapy.

The occurrence of infectious diseases in mixed farming of domesticated wild herbivores and livestock in Kenya. II. Bacterial diseases.

The prevalence of antibodies to Brucella spp., Mycobacterium paratuberculosis and the Mycoplasma spp. causing contagious bovine pleuropneumonia and contagious caprine pleuropneumonia was determined in various species of ruminants on a ranch in the semi-arid zone of southeastern Kenya. Antibody titers to Brucella spp. were found in eland (Taurotragus oryx), oryx (Oryx beisa) and camels (Camelus dromedarius). Reactors were not found in buffalo (Syncerus caffer), sheep (Ovis aries) and goats (Capra hircus). Brucella sp. was not isolated from eland and camels. Antibody titers to M. paratuberculosis were found only in camels and goats. Mycobacteria were not detected in feces of two serologically positive camels. Significant serum antibody titers to Mycoplasma mycoides mycoides were found only in camels. Antibody titers to Mycoplasma sp. (strain F38), which causes contagious caprine pleuropneumonia, were found in buffalo, cattle and camels but not in the other species. Attempts to isolate the Mycoplasma sp. from nasal secretion of the buffalo and camels failed. The possible occurrence of tuberculosis in camels is discussed. Under the conditions at the ranch, contagious bacterial diseases appear to be of minor importance in the domesticated wild herbivores. The introduced camels, however, might be a source of various infections such as brucellosis, mycoplasmosis and possibly tuberculosis for the other susceptible species.