Immune phenotypes and checkpoint molecule expression of clonally expanded lymph node-infiltrating T cells in classical Hodgkin lymphoma

Lymph node-infiltrating T cells have been of particular interest in classical Hodgkin lymphoma (cHL). High rates of complete therapeutic responses to antibody-mediated immune checkpoint blockade, even in relapsed/refractory patients, suggest the existence of a T cell-dominated, antigen-experienced, functionally inhibited and lymphoma-directed immune microenvironment. We asked whether clonally expanded T cells (1) were detectable in cHL lymph nodes, (2) showed characteristic immune phenotypes, and (3) were inhibited by immune checkpoint molecule expression. We applied high-dimensional FACS index sorting and single cell T cell receptor αβ sequencing to lymph node-infiltrating T cells from 10 treatment-naïve patients. T cells were predominantly CD4(+) and showed memory differentiation. Expression of classical immune checkpoint molecules (CTLA-4, PD-1, TIM-3) was generally low (< 12.0% of T cells) and not different between CD4(+) and CD8(+) T cells. Degrees of clonal T cell expansion varied between patients (range: 1-18 expanded clones per patient) and was almost exclusively restricted to CD8(+) T cells. Clonally expanded T cells showed non-naïve phenotypes and low checkpoint molecule expression similar to non-expanded T cells. Our data suggest that the therapeutic effects of immune checkpoint blockade require mechanisms in addition to dis-inhibition of pre-existing lymphoma-directed T cell responses. Future studies on immune checkpoint blockade-associated effects will identify molecular T cell targets, address dynamic aspects of cell compositions over time, and extend their focus beyond lymph node-infiltrating T cells

Lymphocyte predominant cells detect Moraxella catarrhalis-derived antigens in nodular lymphocyte-predominant Hodgkin lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is a rare lymphoma of B-cell origin with frequent expression of functional B-cell receptors (BCRs). Here we report that expression cloning followed by antigen screening identifies DNA-directed RNA polymerase beta' (RpoC) from Moraxella catarrhalis as frequent antigen of BCRs of IgD &lt;sup&gt;+&lt;/sup&gt; LP cells. Patients show predominance of HLA-DRB1*04/07 and the IgVH genes encode extraordinarily long CDR3s. High-titer, light-chain-restricted anti-RpoC IgG1/κ-type serum-antibodies are additionally found in these patients. RpoC and MID/hag, a superantigen co-expressed by Moraxella catarrhalis that is known to activate IgD &lt;sup&gt;+&lt;/sup&gt; B cells by binding to the Fc domain of IgD, have additive activation effects on the BCR, the NF-κB pathway and the proliferation of IgD &lt;sup&gt;+&lt;/sup&gt; DEV cells expressing RpoC-specific BCRs. This suggests an additive antigenic and superantigenic stimulation of B cells with RpoC-specific IgD &lt;sup&gt;+&lt;/sup&gt; BCRs under conditions of a permissive MHC-II haplotype as a model of NLPHL lymphomagenesis, implying future treatment strategies

Prompt K_short production in pp collisions at sqrt(s)=0.9 TeV

The production of K_short mesons in pp collisions at a centre-of-mass energy of 0.9 TeV is studied with the LHCb detector at the Large Hadron Collider. The luminosity of the analysed sample is determined using a novel technique, involving measurements of the beam currents, sizes and positions, and is found to be 6.8 +/- 1.0 microbarn^-1. The differential prompt K_short production cross-section is measured as a function of the K_short transverse momentum and rapidity in the region 0 < pT < 1.6 GeV/c and 2.5 < y < 4.0. The data are found to be in reasonable agreement with previous measurements and generator expectations.Comment: 6+18 pages, 6 figures, updated author lis

Assignment of karyopherin alpha 1 (KPNA1) to human chromosome band 3q21 by in situ hybridization

[No abstract available

Assignment of KPNA4 and KPNB1 encoding karyopherin alpha 4 and beta 1 to human chromosome bands 11q22 and 17q21 respectively, by in situ hybridization

[No abstract available

Assignment of karyopherin alpha 1 (KPNA1) to human chromosome band 3q21 by in situ hybridization

[No abstract available

Expression of activation-induced cytidine deaminase in malignant lymphomas infiltrating the bone marrow.

Somatic hypermutation of immunoglobulin genes and class switch recombination are pivotal processes in the germinal center (GC) reaction and have been implicated in the development of malignant B-cell lymphoma. Both processes require the enzyme activation-induced cytidine deaminase (AID). Expression of AID is largely restricted to GC B cells and B cells that undergo class switch recombination outside the GC. AID is also expressed in many B-cell lymphomas. This study investigates the expression of AID of malignant lymphomas infiltrating the bone marrow. Bone marrow trephines (n=130) with infiltration of Hodgkin lymphoma and non-Hodgkin lymphoma of B cell and T-cell type and trephines with reactive lymphoid follicles (n=16) were analyzed immunohistochemically for AID protein. AID is expressed in bone marrow infiltrates of malignant lymphomas. AID was generally detected in lymphomas of GC origin. Tumor cells of hairy cell leukemia are mostly AID. There is apparently no different expression of AID found in bone marrow infiltrates of malignant lymphomas compared with a control group with nodal malignant lymphoma infiltrates (n=105). These results suggest that the expression pattern of AID in lymphoma infiltrates in the bone marrow reflects that of extramedullary lymphoma infiltrates