Co-sensitization graph of TLP allergens.

<p>Each node represents one allergen (TLP as white ellipses, non-TLP allergens as blue square nodes, and LTP-allergen Pru p 3 as a green diamond) and the links represent co-sensitization of one or more sera for the linked allergens. The weight of each link, ranging between 0 and 1, measures the degree of co-sensitization. For the sake of clarity, only the 25 links of weight greater than 0.50 out of the total 253 existing links were plotted.</p

Frequency of sensitization in the different geographical areas using the homemade microarray and sera from fruit-allergic (FAG) patients, and non-food pollen-allergic (PAG) subjects.

<p>Only TLPs with more than 10% positive response were represented: Pru p 2.0201, Pru p 2.0101, chestnut, plane, lettuce and cabbage TLPs.</p

Pollen counts (grains/m³ of air) of the regions included in the study.

<p>Data were obtained as the average of the previous n years, from the Comité de Aerobiología-SEAIC (<a href="http://www.polenes.com/concentraciones.html" target="_blank">http://www.polenes.com/concentraciones.html</a>) and from PIA-Punto de información de Aerobiología-UAB (<a href="http://lap.uab.cat/aerobiologia/" target="_blank">http://lap.uab.cat/aerobiologia/</a>).</p>*<p>Average of pollen counts (grains/m³). The time period is indicated in brackets.</p

Average weight of allergens included in the co-sensitization graph.

<p>Average weight of allergens included in the co-sensitization graph.</p

Characteristics of the patient sample.

1<p>Total, all patients;</p>2<p>FAG, Fruit-allergic patients;</p>3<p>PAG, Pollen-allergic food-tolerant patients;</p>4<p>M, male; F, female;</p>*<p>SPTs with purified protein were performed in a selected group of patients of 50 FAG, 20 PAG and 20 non-pollen food-tolerant subjects.</p

Frequency of sensitization obtained by the TLP microarray using sera from both fruit-allergic (FAG) patients, and non-food pollen allergic (PAG) subjects.

<p>Odds ratios are presented in parentheses (95% CI; <i>p</i><0.001).</p

IgE binding inhibition of the TLP microarray, when serum pool (n = 21; three per area) or individual sera were preincubated for 3 h at room temperature with increasing amounts of Pru p 2.0201, and chestnut and plane -pollen TLPs.

<p>IgE binding inhibition of the TLP microarray, when serum pool (n = 21; three per area) or individual sera were preincubated for 3 h at room temperature with increasing amounts of Pru p 2.0201, and chestnut and plane -pollen TLPs.</p

Intra-tumoral and peripheral blood TIGIT and PD-1 as immune biomarkers in nodular lymphocyte predominant Hodgkin lymphoma

In classical Hodgkin lymphoma (cHL), responsiveness to immune-checkpoint block?ade (ICB) is associated with specific tumor microenvironment (TME) and peripheral blood features. The role of ICB in nodular lymphocyte predominant Hodgkin lym?phoma (NLPHL) is not established. To gain insights into its potential in NLPHL, we compared TME and peripheral blood signatures between HLs using an integrative multiomic analysis. A discovery/validation approach in 121 NLPHL and 114 cHL patients highlighted >2-fold enrichment in programmed cell death-1 (PD-1) and T-cell Ig and ITIM domain (TIGIT) gene expression for NLPHL versus cHL. Multiplex imaging showed marked increase in intra-tumoral protein expression of PD-1+ (and/or TIGIT+) CD4+ T-cells and PD-1+CD8+ T-cells in NLPHL compared to cHL. This included T-cells that rosetted with lymphocyte predominant (LP) and Hodgkin Reed–Sternberg (HRS) cells. In NLPHL, intra-tumoral PD-1+CD4+ T-cells frequently expressed TCF-1, a marker of heightened T-cell response to ICB. The peripheral blood signatures between HLs were also distinct, with higher levels of PD-1+TIGIT+ in TH1, TH2, and regulatory CD4+ T-cells in NLPHL versus cHL. Circulating PD-1+CD4+ had high levels of TCF-1. Notably, in both lymphomas, highly expanded populations of clonal TIGIT+PD-1+CD4+ and TIGIT+PD-1+CD8+ T-cells in the blood were also present in the TME, indicating that immune-checkpoint expressing T-cells circulated between intra-tumoral and blood compartments. In in vitro assays, ICB was capable of reducing rosette formation around LP and HRS cells, suggesting that disruption of rosetting may be a mechanism of action of ICB in HL. Overall, results indicate that further evaluation of ICB is warranted in NLPHL.</p