Divergent response to radio-immunotherapy is defined by intrinsic features of the tumor microenvironment.

Background: Treatment with immunotherapy can elicit varying responses across cancer types, and the mechanistic underpinnings that contribute to response vrsus progression remain poorly understood. However, to date there are few preclinical models that accurately represent these disparate disease scenarios.

Methods: Using combinatorial radio-immunotherapy consisting of PD-1 blockade, IL2Rβγ biased signaling, and OX40 agonism we were able to generate preclinical tumor models with conflicting responses, where head and neck squamous cell carcinoma (HNSCC) models respond and pancreatic ductal adenocarcinoma (PDAC) progresses.

Exposure to Pseudomonas spp. increases Anopheles gambiae insecticide resistance in a host-dependent manner.

The microbiota of mosquitoes influences many aspects of their biology, including developmental processes, mating and sexual reproduction, immune functions, and refractoriness to pathogens. Here, we considered their role in resistance against insecticides. In particular, we assessed how larval infection of a permethrin-resistant and a sensitive colony of Anopheles gambiae by four strains belonging to three different Pseudomonas species affects several life history traits and the impact of the insecticide on adult mortality.

Regional cerebral perfusion and sympathetic activation during exercise in hypoxia and hypercapnia: preliminary insight into 'Cushing's mechanism'.

We examined the interactive influence of hypoxia and exercise, and hypercapnia and exercise, on regional cerebral perfusion and sympathetic activation. Twenty healthy young adults (seven women) completed study trials including (1) rest in normoxia ( : ∼96%, : ∼36 mmHg), normocapnic hypoxia ( : ∼84%, : ∼36 mmHg), and normoxic hypercapnia ( : ∼98%, : ∼46 mmHg) and (2) unilateral rhythmic handgrip exercise (45% of maximal voluntary contraction at 1 Hz for 3 min) under the same gas conditions. Based on the exercising arm, blood flow in the contralateral internal carotid (ICA) and ipsilateral vertebral (VA) arteries, anterior and posterior cerebral O delivery ( ), and muscle sympathetic nerve activity (MSNA) were measured in each trial.

IL15/IL15Rα complex induces an anti-tumor immune response following radiation therapy only in the absence of Tregs and fails to induce expansion of progenitor TCF1+ CD8 T cells.

Background: This work seeks to understand whether IL15-incorporating treatments improve response to radiotherapy and uncover mechanistic rationale for overcoming resistance to IL15 agonism using novel therapeutic combinations.

Experimental Design: Orthotopic tumor models of PDAC were used to determine response to treatment. IL15-/- and Rag1-/- mouse models were employed to determine dependence on IL15 and CTLs, respectively.