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

Short and Long-Term Impacts of Biotechnology Education on Professionals Who Communicate Science to the Public

Consumer acceptance or rejection of biotechnology is often shaped by information prepared by communicators with varying levels of scientific knowledge, awareness, and acceptance. This study compared the prior, post-workshop, and sustained (1 year) biotechnology awareness, acceptance, and attitudes of professionals who communicate biotechnology to the public at an informational, day-long, university-sponsored workshop. Thirty-seven participants completed the three rounds of data collection. They consistently rated their scientific knowledge high. Throughout the three rounds, their primary media source of biotechnology information was newspapers, with the web being the second most frequently cited source. Participants were somewhat accepting of genetic modification of microorganisms, forests/landscape plants, and food crops, but were somewhat unaccepting of genetic modification of animals and humans. Fear of genes moving unchecked to other plants, insects, or microorganisms; fear of environmental harm; and fear of food safety consequences were identified as obstacles to their acceptance of food biotechnology. Participants were most confident with statements related to biotechnology from university scientists and health professionals and least confident with statements from celebrities. They saw their professional role in providing analysis and interpretation regarding desirable and undesirable consequences of biotechnology as important. Although the study participants were professionals, their awareness and attitudes toward biotechnology were similar to consumer awareness and attitudes measured in previous studies. It is important that university scientists provide unbiased, research-based biotechnology information to those who communicate biotechnology to the public (e.g., through workshops, websites, etc.) and accommodate learners with varying levels of scientific knowledge, because these communicators will affect consumer attitudes

Second-generation tyrosine kinase inhibitors improve the survival of patients with chronic myeloid leukemia in whom imatinib therapy has failed

<p><b>Background:</b> It has not been clearly established whether second-generation tyrosine kinase inhibitors actually improve the survival of patients with chronic myeloid leukemia in chronic phase who are given nilotinib or dasatinib therapy after treatment failure with imatinib.</p> <p><b>Design and Methods:</b> To address this issue we compared the survival of 104 patients in whom first-line therapy with imatinib failed and who were then treated with second-generation tyrosine kinase inhibitors with the outcome of 246 patients in whom interferon-a therapy failed and who did not receive tyrosine kinase inhibitor therapy.</p> <p><b>Results:</b> Patients treated with second-generation tyrosine kinase inhibitors had longer overall survival than the interferon controls (adjusted relative risk = 0.28, P = 0.0001). However this survival advantage was limited to the 64.4% of patients in whom imatinib failed but who achieved complete cytogenetic response with the subsequent tyrosine kinase inhibitor (adjusted relative risk = 0.05, P = 0.003), whereas the 35.6% of patients who failed to achieve complete cytogenetic response on the second or third inhibitor had similar overall survival to that of the controls (adjusted relative risk = 0.76, P = 0.65).</p> <p><b>Conclusions:</b> Patients in whom imatinib treatment fails who receive sequential therapy with second-generation tyrosine kinase inhibitors have an enormous advantage in survival over controls (palliative therapy); this advantage is, however, limited to the majority of the patients who achieve a complete cytogenetic response.</p&gt

Proteomic biomarkers for the prediction of transition to psychosis in individuals at clinical high risk: a multi-cohort model development study

Psychosis risk prediction is one of the leading challenges in psychiatry. Previous investigations have suggested that plasma proteomic data may be useful in accurately predicting transition to psychosis in individuals at clinical high risk (CHR). We hypothesized that an a priori-specified proteomic prediction model would have strong predictive accuracy for psychosis risk and aimed to replicate longitudinal associations between plasma proteins and transition to psychosis. This study used plasma samples from participants in 3 CHR cohorts: the North American Prodrome Longitudinal Studies 2 and 3, and the NEURAPRO randomized control trial (total n = 754). Plasma proteomic data were quantified using mass spectrometry. The primary outcome was transition to psychosis over the study follow-up period. Logistic regression models were internally validated, and optimism-corrected performance metrics derived with a bootstrap procedure. In the overall sample of CHR participants (age: 18.5, SD: 3.9; 51.9% male), 20.4% (n = 154) developed psychosis within 4.4 years. The a priori-specified model showed poor risk-prediction accuracy for the development of psychosis (C-statistic: 0.51 [95% CI: 0.50, 0.59], calibration slope: 0.45). At a group level, Complement C8B, C4B, C5, and leucine-rich α-2 glycoprotein 1 (LRG1) were associated with transition to psychosis but did not surpass correction for multiple comparisons. This study did not confirm the findings from a previous proteomic prediction model of transition from CHR to psychosis. Certain complement proteins may be weakly associated with transition at a group level. Previous findings, derived from small samples, should be interpreted with caution

It Is Time To Take A Stand For Medical Research And Against Terrorism Targeting Medical Scientists

Terrorists are attacking scientists who are attempting to alleviate human suffering. We need a concerted public effort to eliminate these acts, particularly the harassment of scientists studying nonhuman primates. This need is highlighted by the attacks upon the home of our friend and colleague, the noted medical scientist, Dr. Edythe London, professor of psychiatry and biobehavioral sciences and of molecular and medical pharmacology at the David Geffen School of Medicine at the University of California Los Angeles (UCLA). Her work exemplifies the unique role of research involving nonhuman primates in enabling the results of research in simple systems (oocytes, cell culture) and lower organisms to be applied to human diseases. The importance of Dr. London’s research was highlighted in a public letter issued on February 8, 2008 from the Director of the National Institutes of Health (NIH), Dr. Elias Zerhouni, who stated, “her work is a prime example of NIH’s efforts … to develop effective treatments for people suffering from addiction—a disease that devastates individuals, families, communities, and costs society more than half a trillion dollars annually in health and crime-related costs and losses in productivity.