Vanishing lines in generalized Adams spectral sequences are generic

We show that in a generalized Adams spectral sequence, the presence of a vanishing line of fixed slope (at some term of the spectral sequence, with some intercept) is a generic property.Comment: 11 pages. Published copy, also available at http://www.maths.warwick.ac.uk/gt/GTVol3/paper7.abs.htm

The Leander McCormick Observatory of the University of Virginia

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The Ice Palace at St. Paul

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The Sturgeon Fishery

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Smash products for secondary homotopy groups

We construct a smash product operation on secondary homotopy groups yielding the structure of a lax symmetric monoidal functor. Applications on cup-one products, Toda brackets and Whitehead products are considered. In particular we prove a formula for the crossed effect of the cup-one product operation on unstable homotopy groups of spheres which was claimed by Barratt-Jones-Mahowald.Comment: We give a clearer description of the tensor product of symmetric sequences of quadratic pair module

Inhibiting tryptophan metabolism enhances interferon therapy in kidney cancer.

Renal cell carcinoma (RCC) is increasing in incidence, and a complete cure remains elusive. While immune-checkpoint antibodies are promising, interferon-based immunotherapy has been disappointing. Tryptophan metabolism, which produces immunosuppressive metabolites, is enhanced in RCC. Here we show indolamine-2,3-dioxygenase-1 (IDO1) expression, a kynurenine pathway enzyme, is increased not only in tumor cells but also in the microenvironment of human RCC compared to normal kidney tissues. Neither kynurenine metabolites nor IDO inhibitors affected the survival or proliferation of human RCC or murine renal cell adenocarcinoma (RENCA) cells in vitro. However, interferon-gamma (IFNγ) induced high levels of IDO1 in both RCC and RENCA cells, concomitant with enhanced kynurenine levels in conditioned media. Induction of IDO1 by IFNα was weaker than by IFNγ. Neither the IDO1 inhibitor methyl-thiohydantoin-DL-tryptophan (MTH-trp) nor IFNα alone inhibited RENCA tumor growth, however the combination of MTH-trp and IFNα reduced tumor growth compared to IFNα. Thus, the failure of IFNα therapy for human RCC is likely due to its inability to overcome the immunosuppressive environment created by increased IDO1. Based on our data, and given that IDO inhibitors are already in clinical trials for other malignancies, IFNα therapy with an IDO inhibitor should be revisited for RCC