Antibodies against endogenous retroviruses promote lung cancer immunotherapy

B cells are frequently found in the margins of solid tumours as organized follicles in ectopic lymphoid organs called tertiary lymphoid structures (TLS)1,2. Although TLS have been found to correlate with improved patient survival and response to immune checkpoint blockade (ICB), the underlying mechanisms of this association remain elusive1,2. Here we investigate lung-resident B cell responses in patients from the TRACERx 421 (Tracking Non-Small-Cell Lung Cancer Evolution Through Therapy) and other lung cancer cohorts, and in a recently established immunogenic mouse model for lung adenocarcinoma3. We find that both human and mouse lung adenocarcinomas elicit local germinal centre responses and tumour-binding antibodies, and further identify endogenous retrovirus (ERV) envelope glycoproteins as a dominant anti-tumour antibody target. ERV-targeting B cell responses are amplified by ICB in both humans and mice, and by targeted inhibition of KRAS(G12C) in the mouse model. ERV-reactive antibodies exert anti-tumour activity that extends survival in the mouse model, and ERV expression predicts the outcome of ICB in human lung adenocarcinoma. Finally, we find that effective immunotherapy in the mouse model requires CXCL13-dependent TLS formation. Conversely, therapeutic CXCL13 treatment potentiates anti-tumour immunity and synergizes with ICB. Our findings provide a possible mechanistic basis for the association of TLS with immunotherapy response

Synthesis of 2,2,4-trimethyl-1,2-dihydroquinolinyl substituted 1,2,3-triazole derivatives: their evaluation as potential PDE 4B inhibitors possessing cytotoxic properties against cancer cells

The 2,2,4-trimethyl-1,2-dihydroquinolinyl substituted 1,2,3-triazole derivatives were designed as potential inhibitors of PDE4B. These compounds were synthesized via a multi-step sequence consisting of copper-catalyzed azide-alkyne cycloaddition (CuAAC) as a key step in aqueous media. The required alkynes were prepared from nimesulide via N-propargylation and then nitro group reduction followed by a CAN mediated modified Skraup reaction of the resulting amine. All the synthesized compounds showed PDE4B inhibitory properties in vitro at 30 μM with two compounds showing >50% inhibition that were supported by the in silico docking results of these compounds at the active site of PDE4B. Three of these PDE4 inhibitors showed promising cytotoxic properties against A549 human lung cancer cells in vitro with IC50 ∼8-9 μM

Molecular breeding tools improved drought tolerant groundnut variety for resistance to foliar fungal diseases

A largely rainfed crop in India, drought tolerance, particularly mid- and end-season tolerance, is a key trait in groundnut varieties. A combination of both empirical and trait-based approaches was used in breeding programs of ICAR and ICRISAT, resulting in release of few tolerant varieties that have superior pod yield under drought stress and/or have enhanced water-use-efficiency. There is a need to breed varieties with drought tolerance, disease resistance and quality traits that suit different production ecologies as well as meet the needs of the farmers, consumers and industries. ICRISAT has released an early-maturing (90-95 d) and drought- tolerant variety ICGV 91114 for the drought-prone Ananthapur district of Andhra Pradesh, India, where about 0.7 m ha area is under groundnut cultivation and has low (300 mm) and erratic (30-40 rainy days) rainfall. On-farm studies conducted with ICGV 91114 during 2008-10 showed 30% reduction in yield variability over the years. Following screening in hot-spots of both rust and LLS disease during 2014 rainy season, a total of 27 introgression lines derived from ICGV 91114 were selected and advanced for evaluation in multi-location trials at six locations in 2015 under rainfed conditions. Based on the pod yield under rainfed conditions and disease resistance, three superior introgression lines (ICGV 14410, ICGV 13189, ICGV 14421) were proposed for the first-ever NILs trial (near-isogenic lines trial) along with eight others conducted under All India Coordinated Research Project on Groundnut (AICRP-G) at national level

G × E interactions in QTL introgression lines of Spanish-type groundnut (Arachis hypogaea L.)

Multi-environment testing at five locations for rust and late leaf spot (LLS) resistance with 41 introgressed lines (ILs) bred using marker-assisted backcross breeding in the genetic background Spanish-type groundnut varieties identified significant genotype, and genotype × environment interactions (GEI) for LLS disease resistance and yield parameters. Significant GEI effects suggest the need to identify location specific breeding lines to achieve gains in pod yield and LLS resistance. The observed variable LLS disease reaction among the ILs in part suggests influence of background genotype on the level of resistance. A breeding scheme with early generation selection using molecular markers followed by phenotyping for LLS, and multi-location testing of fixed breeding lines was optimized to enhance selection intensity and accuracy in groundnut breeding. The ILs, ICGVs 14431, 14436 and 14438 with pooled LLS score at 90 DAS of 3.5–3.7 were superior to respective recurrent parent for pod yield, with early maturing similar to recurrent parents. The pod yield advantage in ILs is attributed by more number of pods, besides resistance to LLS that contributes to better filling