Microenvironmental immune cell alterations across the spectrum of nodular lymphocyte predominant Hodgkin lymphoma and T-cell/histiocyte-rich large B-cell lymphoma

BACKGROUND: The clinicopathological spectrum of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL), also known as nodular lymphocyte predominant B-cell lymphoma, partially overlaps with T-cell/histiocyte-rich large B-cell lymphoma (THRLCBL). NLPHL histology may vary in architecture and B-cell/T-cell composition of the tumour microenvironment. However, the immune cell phenotypes accompanying different histological patterns remain poorly characterised. METHODS: We applied a multiplexed immunofluorescence workflow to identify differential expansion/depletion of multiple microenvironmental immune cell phenotypes between cases of NLPHL showing different histological patterns (as described by Fan et al, 2003) and cases of THRLBCL. RESULTS: FOXP3-expressing T-regulatory cells were conspicuously depleted across all NLPHL cases. As histology progressed to variant Fan patterns C and E of NLPHL and to THRLBCL, there were progressive expansions of cytotoxic granzyme-B-expressing natural killer and CD8-positive T-cells, PD1-expressing CD8-positive T-cells, and CD163-positive macrophages including a PDL1-expressing subset. These occurred in parallel to depletion of NKG2A-expressing natural killer and CD8-positive T-cells. DISCUSSION: These findings provide new insights on the immunoregulatory mechanisms involved in NLPHL and THLRBCL pathogenesis, and are supportive of an increasingly proposed biological continuum between these two lymphomas. Additionally, the findings may help establish new biomarkers of high-risk disease, which could support a novel therapeutic program of immune checkpoint interruption targeting the PD1:PDL1 and/or NKG2A:HLA-E axes in the management of high-risk NLPHL and THRLBCL

An action for F-theory: SL(2)R+ exceptional field theory

DSB is supported by the STFC grant ST/L000415/1 'String Theory, Gauge Theory and Duality'. CB is supported in part by the Belgian Federal Science Policy Office through the Interuniversity Attraction Pole P7/37 'Fundamental Interactions', and in part by the 'FWO-Vlaanderen' through the project G.0207.14N and by the Vrije Universiteit Brussel through the Strategic Research Program 'High-Energy Physics'. EM is supported by the ERC Advanced Grant "Strings and Gravity' (Grant No. 32004). FJR is supported by an STFC studentship

The Spectrum of Goldstini and Modulini

When supersymmetry is broken in multiple sectors via independent dynamics, the theory furnishes a corresponding multiplicity of "goldstini" degrees of freedom which may play a substantial role in collider phenomenology and cosmology. In this paper, we explore the tree-level mass spectrum of goldstini arising from a general admixture of F-term, D-term, and almost no-scale supersymmetry breaking, employing non-linear superfields and a novel gauge fixing for supergravity discussed in a companion paper. In theories of F-term and D-term breaking, goldstini acquire a mass which is precisely twice the gravitino mass, while the inclusion of no-scale breaking renders one of these modes, the modulino, massless. We argue that the vanishing modulino mass can be explained in terms of an accidental and spontaneously broken "global" supersymmetry.Comment: 10 pages, 2 figures; v2: typo corrected, references updated; v3: version to appear in JHE

Effective Symmetries of the Minimal Supermultiplet of N = 8 Extended Worldline Supersymmetry

A minimal representation of the N = 8 extended worldline supersymmetry, known as the `ultra-multiplet', is closely related to a family of supermultiplets with the same, E(8) chromotopology. We catalogue their effective symmetries and find a Spin(4) x Z(2) subgroup common to them all, which explains the particular basis used in the original construction. We specify a constrained superfield representation of the supermultiplets in the ultra-multiplet family, and show that such a superfield representation in fact exists for all adinkraic supermultiplets. We also exhibit the correspondences between these supermultiplets, their Adinkras and the E(8) root lattice bases. Finally, we construct quadratic Lagrangians that provide the standard kinetic terms and afford a mixing of an even number of such supermultiplets controlled by a coupling to an external 2-form of fluxes.Comment: 13 Figure

Prognostic indices in diffuse large B-cell lymphoma in the rituximab era: an analysis of the UK National Cancer Research Institute R-CHOP 14 versus 21 phase 3 trial

We compared the International Prognostic Index (IPI), Revised (R)‐IPI and age‐adjusted (aa)‐IPI as prognostic indices for patients with diffuse large B‐cell lymphoma (DLBCL) in the UK National Cancer Research Institute (NCRI) R‐CHOP 14 versus 21 trial (N = 1080). The R‐IPI and aa‐IPI showed no marked improvement compared to the IPI for overall and progression‐free survival, in terms of model fit or discrimination. Similar results were observed in exploratory analyses incorporating the Grupo Español de Linfomas/Transplante de Médula Ósea (GELTAMO)‐IPI, where baseline β2‐microglobulin data were available (N = 655). Although our findings support current use of the IPI, a novel prognostic tool to better delineate a high‐risk DLBCL group in the rituximab era is needed