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Checkpoint inhibition (CPI) therapy and adoptive cell therapy with autologous tumor-infiltrating lymphocytes (TIL-based ACT) are the two most effective immunotherapies for the treatment of metastatic melanoma. While CPI has been the dominating therapy in the past decade, TIL-based ACT is beneficial for individuals even after progression on previous immunotherapies. Given that notable differences in response have been made when used as a subsequent treatment, we investigated how the qualities of TILs changed when the ex vivo microenvironment of intact tumor fragments were modulated with checkpoint inhibitors targeting programmed death receptor 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). Initially, we show that unmodified TILs from CPI-resistant individuals can be produced, are overwhelmingly terminally differentiated, and are capable of responding to tumor. We then investigate these properties in ex vivo checkpoint modulated TILs finding that that they retain these qualities. Lastly, we confirmed the specificity of the TILs to the highest responding tumor antigens, and identified this reactivity resides largely in CD39 + CD69 + terminally differentiated populations. Overall, we found that anti-PD-1 will alter the proliferative capacity while anti-CTLA4 will influence breadth of antigen specificity., Competing Interests: IMS has lectured for or had advisory board relationships with MSD, Sanofi Aventis, BMS, Pierre Fabre, Novartis, TILT Biotherapeutics, IO Biotech, and Novo Nordisk. IS has received research grants from Lytix biopharma, IO Biotech, BMS, Adaptimmune, and TILT Biotherapeutics. IS is a co-founder and shareholder for the company IO Biotech. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor NO declared a shared parent affiliation with the authors TH, CF, JG, TB, MP, MD, MA, IMS and OM at the time of review., (Copyright © 2023 Hulen, Friese, Kristensen, Granhøj, Borch, Peeters, Donia, Andersen, Hadrup, Svane and Met.)

Background: To reduce the risk of invasive aspergillosis (IA), air purification by high-efficiency particulate air filtration and laminar air flow (HEPA/LAF) is standard of care in allogeneic blood stem cell transplantation. Its use in non-transplant haematological patients is inconsistent., Objectives: We sought to assess the incidence and outcome of pulmonary IA in non-transplant patients with life-threatening neutropenia by comparing an ambient air hospitalisation period (2008-2011) with a subsequent HEPA/LAF hospitalisation period (2012-2014)., Patients and Methods: We compared 204 consecutive patients with acute myeloid leukaemia, acute lymphoblastic leukaemia or aplastic anaemia completing 534 neutropenia-related hospitalisations under ambient air conditions with 126 such patients completing 437 neutropenia-related hospitalisations under HEPA/LAF conditions. IA was defined using the 2008 EORTC/MSG criteria., Results: Within a 7-year study period, we observed one 'proven', three 'probable' and 73 'possible' IAs, most often during acute leukaemia remission induction. Their frequency rose with increasing duration of life-threatening neutropenia (1-10 days, 1.8%; >40 days, 35.2%) and concomitant severe anaemia (0 days, 3.2%; >20 days, 31.0%). Multiple logistic regression revealed a strong correlation between IA incidence and hospitalisation under HEPA/LAF conditions (odds ratio [OR], 0.368 [95% confidence interval, 0.207-0.654]; p < .001) and duration of neutropenia (OR, 1.043 [1.023-1.062] per day; p < .001) and anaemia (OR, 1.044 [1.008-1.081] per day; p = .016). IA-associated fatal outcomes were non-significantly reduced under HEPA/LAF (OR, 0.077 [0.005-1.151]; p = .063). The protective effect of HEPA/LAF was not seen under posaconazole prophylaxis (OR, 0.856 [0.376-1.950]; p = .711)., Conclusions: Implementation of HEPA/LAF was associated with a significant reduction in neutropenia-related IA in non-transplant haematological patients., (© 2023 The Authors. Mycoses published by Wiley-VCH GmbH.)

Objective: Oral anticancer agents (OAAs) are associated with side effects that interfere with medication adherence, despite patient education regarding side effect management. Video reflexive ethnography (VRE) captures care processes on video that allow participants to learn from videos. The purpose of this pilot study was to assess the usefulness and impact of VRE on improving OAA education., Methods: This qualitative study was conducted in a pharmacist-managed OAA clinic: two pharmacists and four patients participated. We filmed each pharmacist providing education to two patients. We conducted patient interviews and one reflexivity session with both pharmacists to learn participants' perspectives. We used thematic content analysis to analyze data., Results: Two themes emerged: what patients liked/helped, and things that were unclear. Patients liked instructions on temperature taking, directions to safely handle and store OAAs. Unclear areas included knowing the timing of the worst side effects.During the reflexivity session, pharmacists found patients' comments useful to improve their practice., Conclusion: VRE was acceptable to pharmacists and patients. Pharmacists recognized VRE as a helpful technique to improve patient education on OAAs., Innovation: The use of video enables participants to scrutinize and reshape their practices, making VRE a powerful innovation and adjunct to quality improvement initiatives., Competing Interests: The authors have no completing interests to declare., (© 2023 The Authors.)

This paper investigates the 'cynical scientist' as a figure in British animal science discourse that developed in relation to the nineteenth-century emergence of the 'sceptical scientist'. Here, efforts by scientists to demarcate their profession's territory led to religious backlash against an alleged 'divorce' of British science from Christian morality. Animal experimentation became embroiled in this controversy through antivivisectionists' conviction that animal research was symptomatic of scientific scepticism and Continental atheism's malign influence. Accusations of cynicism ultimately forced British scientists to accept legal regulation following the 1875 Royal Commission on Vivisection. British scientists were, however, able to utilise their political leverage and credibility as experts to favourably influence licensing and inspection. We suggest that efforts to silence public claims of scientific cynicism may have enabled 'cynical scientists' to remain invisible and that this was marked by privilege and power, not marginality. Nevertheless, we argue that regulation and reforms have also worked to internalise within British animal science the notion that scientific cynicism must be combatted through proper governance and internal discipline., Competing Interests: Conflict of interestThe authors do not have any competing interests—intellectual or financial—in the research detailed in the manuscript., (© The Author(s) 2023.)

Background: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer., Patients and Methods: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19)., Results: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19., Conclusions: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future., Competing Interests: Disclosure ALS reports non-financial support from Astellas, non-financial support from Pfizer, outside the submitted work. CL reports research support from Genentech/imCORE, outside the submitted work. ZB reports non-financial support from Bristol Myers Squibb, grants from Genentech/imCORE, personal fees from UpToDate, outside the submitted work. CYH reports personal fees from NashBio, outside the submitted work. SAB reports personal fees from Exelixis, personal fees from Seattle Genetics, personal fees from Pfizer, personal fees from Bristol Myers Squibb, outside the submitted work. CRF reports research grants from the Merck Foundation and National Comprehensive Cancer Network (NCCN)/Pfizer, outside the submitted work. EAG reports personal fees and other from Alexion Pharmaceuticals, personal fees and non-financial support from Novartis Pharmaceuticals, personal fees, non-financial support and other from Astex/Otsuka Pharmaceuticals, other from Apellis Pharmaceuticals, personal fees, non-financial support, and other from Celgene/Bristol Myers Squibb, grants and personal fees from AbbVie/Genentech, other from Celldex Therapeutics, personal fees from Boston Biomedical, outside the submitted work. JEH reports research funding paid to her institution from Dendreon Pharmaceuticals LLC, research funding paid to her institution from Regeneron Pharmaceuticals, personal fees from Genzyme, personal fees from Seagen, outside the submitted work. RRM reports grants and personal fees from Bayer, grants from Pfizer, grants from Tempus, personal fees from AVEO, personal fees from Caris, personal fees from Bristol Myers Squib, personal fees from Exelixis, personal fees from Janssen, personal fees from Novartis, personal fees from Pfizer, personal fees from Sanofi, personal fees from Tempus, personal fees from Dendreon, personal fees from Vividion, personal fees from AstraZeneca, personal fees from Calithera, personal fees from Merck, outside the submitted work. OAP reports personal fees from International Consulting Associates, Inc., outside the submitted work. EMW-B reports personal fees from Astellas, personal fees from AVEO Oncology, personal fees from Bristol Myers Squibb, other from Exelixis, grants from Pfizer Global Medical Grants, other from Nektar, other from Immunomedics, outside the submitted work. SM reports personal fees from National Geographic, outside the submitted work. DF reports a grant from Merck to study COVID-19 in immunocompromised patients, outside of the submitted work. YS reports personal fees from Novartis, personal fees from Roche, personal fees from Pfizer, personal fees from Janssen, personal fees from Eisai, personal fees from AstraZeneca, outside of the submitted work. JLW reports personal fees from Westat, personal fees from Roche, personal fees from Melax Tech, personal fees from Flatiron Health, other from HemOnc.org LLC (ownership), outside the submitted work. TKC reports institutional and personal, paid and unpaid support for research, advisory boards, consultancy, and honoraria from AstraZeneca, Aravive, Aveo, Bayer, Bristol Myers Squibb, Eisai, EMD Serono, Exelixis, GlaxoSmithKline, IQVIA, Ipsen, Kanaph, Lilly, Merck, Nikang, Novartis, Pfizer, Roche, Sanofi/Aventis, Takeda, Tempest, UpToDate, CME events (Peerview, OncLive and others), outside the submitted work. All other authors have declared no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Galectin-3 (Gal3) can be expressed by many cells in the tumor microenvironment (TME), including cancer cells, cancer-associated fibroblasts, tumor-associated macrophages, and regulatory T cells (Tregs). In addition to immunosuppression, Gal3 expression has been connected to malignant cell transformation, tumor progression, and metastasis. In the present study, we found spontaneous T-cell responses against Gal3-derived peptides in PBMCs from both healthy donors and cancer patients. We isolated and expanded these Gal3-specific T cells in vitro and showed that they could directly recognize target cells that expressed Gal3. Finally, therapeutic vaccination with a long Gal3-derived peptide epitope, which induced the expansion of Gal3-specific CD8 + T cells in vivo , showed a significant tumor-growth delay in mice inoculated with EO771.LMB metastatic mammary tumor cells. This was associated with a significantly lower percentage of both Tregs and tumor-infiltrating Gal3 + cells in the non-myeloid CD45 + CD11b - compartment and with an alteration of the T-cell memory populations in the spleens of Gal3-vaccinated mice. These results suggest that by activating Gal3-specific T cells by an immune-modulatory vaccination, we can target Gal3-producing cells in the TME, and thereby induce a more immune permissive TME. This indicates that Gal3 could be a novel target for therapeutic cancer vaccines., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)