Rapid temperature responses of photosystem II efficiency forecast genotypic variation in rice vegetative heat tolerance

This article is protected by copyright. All rights reserved. ACKNOWLEDGEMENTS We are grateful to the University of Nottingham glasshouse staff for their assistance with general plant maintenance. We thank Laura Briers for supplying the photograph used in Figure 1. This article benefited substantially from the critical insight of Dr Alex Burgess. JNF is supported by the Palaeobenchmarking Resilient Agriculture Systems (PalaeoRAS) project funded by the Future Food Beacon of the University of Nottingham. EHM receives funding from the Biotechnology and Biological Sciences Research Council (BBSRC, grant no. BB/R004633/1). KES is supported by a University of Nottingham–BBSRC Doctoral Training Partnership studentship.Peer reviewedPublisher PD

Recombinant Newcastle disease viruses expressing immunological checkpoint inhibitors induce a pro-inflammatory state and enhance tumor-specific immune responses in two murine models of cancer

IntroductionTumor microenvironments are immunosuppressive due to progressive accumulation of mutations in cancer cells that can drive expression of a range of inhibitory ligands and cytokines, and recruitment of immunomodulatory cells, including myeloid-derived suppressor cells (MDSC), tumor-associated macrophages, and regulatory T cells (Tregs).MethodsTo reverse this immunosuppression, we engineered mesogenic Newcastle disease virus (NDV) to express immunological checkpoint inhibitors anti-cytotoxic T lymphocyte antigen-4 and soluble programmed death protein-1.ResultsIntratumoral administration of recombinant NDV (rNDV) to mice bearing intradermal B16-F10 melanomas or subcutaneous CT26LacZ colon carcinomas led to significant changes in the tumor-infiltrating lymphocyte profiles. Vectorizing immunological checkpoint inhibitors in NDV increased activation of intratumoral natural killer cells and cytotoxic T cells and decreased Tregs and MDSCs, suggesting induction of a pro-inflammatory state with greater infiltration of activated CD8+ T cells. These notable changes translated to higher ratios of activated effector/suppressor tumor-infiltrating lymphocytes in both cancer models, which is a promising prognostic marker. Whereas all rNDV-treated groups showed evidence of tumor regression and increased survival in the CT26LacZ and B16-F10, only treatment with NDV expressing immunological checkpoint blockades led to complete responses compared to tumors treated with NDV only.DiscussionThese data demonstrated that NDV expressing immunological checkpoint inhibitors could reverse the immunosuppressive state of tumor microenvironments and enhance tumor-specific T cell responses