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). 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 elusive. 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 adenocarcinoma. 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

High levels of seed inviability among seven populations of the endangered Short’s goldenrod (Solidago shortii – Asteraceae)

The physical conditions of mature seeds were examined from representatives of six Kentucky populations and one Indiana population of the endangered species Short\u27s goldenrod (Solidago shortii, Asteraceae.) A random sample of seeds from the Kentucky populations revealed the majority (71%-99%) were incapable of successful seedling development, being damaged due to either an insect predator or to unsuccessful fertilization or embryo abortion. Successful seedling development from phenotypically normal seeds ranged from 71% to 96% in the sampled Kentucky populations. The majority of the damaged seeds were necrotic, ranging from 62%-90%. The Indiana population exhibited the lowest level of herbivory (2%) observed for the species. Two congener goldenrod species (S. canadensis var.altissima and S.nemoralis) found growing either within or adjacent to three populations of Short\u27s goldenrod exhibited lower levels of necrosis and higher levels of herbivory. A third congener species (S.gigantea) exhibited equal levels of the two seed conditions (herbivory and necrosis). The influence of seed inviability upon the persistence of natural populations of Short\u27s goldenrod is at present unknown

Risk for post-operative delirium related to comorbidities in older adult cardiac patients: An integrative review

Background: Delirium is defined as a sudden onset of confusion due to disruption in normal brain functioning. Although it is highly prevalent in post-operative patients, most significantly the older adult population, limited information exists explaining why its onset occurs. Purpose: This integrative review aimed to synthesise specific comorbidities that can contribute to the development of post-operative delirium in older adult cardiac surgical patients. Methods: PRISMA statement was used to report the identification, selection, appraisal and synthesis of articles and the PRISMA diagram reports the selection process. The Johns Hopkins Evidence-Based Practice Tools were used as guide in literature review, critical analysis, levelling of evidence and quality rating. PubMed, ProQuest, CINAHL plus, EMBASE, MEDLINE, Ovid Nursing Collection and Cochrane databases were searched from 2015 to 2020. Results: The initial search yielded 1529 articles. Following the removal of duplicates and screening, 14 articles were included for this review. The following comorbidities were identified in the studies: Diabetes mellitus, atrial fibrillation, depression, impaired olfaction, pre-existing cerebrovascular disease, pre-existing cardiovascular disease, insomnia and frailty. Conclusion: There was a strong indication of the development of post-operative delirium among older adult cardiac surgical patients with comorbidities. Relevance to clinical practice: Awareness of the impact of comorbidities in developing post-operative delirium may help healthcare providers to plan and implement proper care management among older adult cardiac surgical patients with comorbidities