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BACKGROUND In Australia, melanoma is managed in primary and secondary care settings. An individual concerned about a suspicious lesion typically presents first to their GP. AIM To identify factors influencing GPs' decisions to diagnose, treat, or refer patients with suspected melanoma. DESIGN & SETTING Semi-structured interviews were undertaken with 23 GPs working in general practice or skin cancer clinics in Australia. METHOD The semi-structured interviews were audio-recorded, de-identified, and professionally transcribed. Thematic analysis was used to analyse the data. RESULTS Considerable variation existed in GPs' self-reported confidence and involvement in melanoma management. Multiple factors were identified as influencing GPs' decisions to diagnose, treat, or refer patients with suspected or confirmed melanoma. Health system level factors included the overlapping roles of GPs and specialists, and access to and/or availability of specialists. Practice level factors included opportunities for formal and informal training, and having a GP with a special interest in skin cancer within their practice. GP and patient level factors included the GP's clinical interests, the clinical features (for example, site and size) and histopathology of the suspected melanoma, eligibility for possible sentinel lymph node biopsy, and patient preferences. For some GPs, concerns over misdiagnosis and the option of referring patients at any stage in the melanoma management continuum appeared to affect their interest and confidence in melanoma management. CONCLUSION GP involvement in melanoma patient care can extend well beyond cancer screening, prevention and supportive care roles to include provision of definitive melanoma patient management. GPs with an interest in being involved in melanoma management should be encouraged and supported to develop the skills needed to manage these patients, and to refer when appropriate. Copyright © 2020, The Authors.BACKGROUND Demand for general practice in the UK is higher than supply. Some patients seek appointments with GPs for minor illnesses rather than self-care. AIM To identify the characteristics of people with a tendency to contact GPs rather than self-care. DESIGN & SETTING A national survey of the British adult population was undertaken in 2018, which included vignettes. METHOD Two vignettes focused on illness in adults half of responders completed a vignette about cough and sore throat for 3 days, and the other half completed a vignette about diarrhoea and vomiting for 2 days. Logistic regression was undertaken to identify characteristics associated with contacting GPs compared with dealing with the problem themselves, calling NHS 111, or contacting another service, including a pharmacist. RESULTS The response rate was 42%, with 2906 responders. Responders were twice as likely to select 'contact GP' for the diarrhoea and vomiting vignette than for the cough and sore throat vignette (44.7% versus 21.8%). Factors associated with tendency for GP contact included being aged >75 years (odds ratio [OR] 2.0, 95% confidence interval [CI] = 1.2 to 3.2); from black, Asian and minority ethnic (BAME) communities (OR 2.1, 95% CI = 1.5 to 3.0); feeling overwhelmed by unexpected health problems (OR 1.4, 95% CI = 0.99 to 2.1); lower health literacy (OR 1.2, 95% CI = 1.0 to 1.4); and believing that general practice is not overused (OR 1.3, 95% CI = 1.1 to 1.7). CONCLUSION Type of symptom, personal characteristics, and population beliefs about general practice utilisation explain the tendency to contact GPs for minor illness amenable to self-care. Copyright © 2020, The Authors.Vaccination of patients against neoantigens expressed in concurrent, recurrent, or tumors developing in individuals at risk of cancer is posing major challenges in terms of which antigens to target and is limited to patients expressing neoantigens in their tumors. Here, we describe a vaccination strategy against antigens that were induced in tumor cells by downregulation of the peptide transporter associated with antigen processing (TAP). Vaccination against TAP downregulation-induced antigens was more effective than vaccination against mutation-derived neoantigens, was devoid of measurable toxicity, and inhibited the growth of concurrent and future tumors in models of recurrence and premalignant disease. Human CD8+ T cells stimulated with TAPlow dendritic cells elicited a polyclonal T-cell response that recognized tumor cells with experimentally reduced TAP expression. Vaccination against TAP downregulation-induced antigens overcame the main limitations of vaccinating against mostly unique tumor-resident neoantigens and could represent a simpler vaccination strategy that will be applicable to most patients with cancer. Copyright ©2020, American Association for Cancer Research.Although understanding of T-cell exhaustion is widely based on mouse models, its analysis in cancer patients could provide clues indicating tumor sensitivity to immune checkpoint blockade (ICB). Data suggest a role for costimulatory pathways, particularly CD28, in exhausted T-cell responsiveness to PD-1/PD-L1 blockade. Here, we used single-cell transcriptomic, phenotypic, and functional approaches to dissect the relation between CD8+ T-cell exhaustion, CD28 costimulation, and tumor specificity in head and neck, cervical, and ovarian cancers. Mizagliflozin concentration We found that memory tumor-specific CD8+ T cells, but not bystander cells, sequentially express immune checkpoints once they infiltrate tumors leading, in situ, to a functionally exhausted population. Exhausted T cells were nonetheless endowed with effector and tumor residency potential but exhibited loss of the costimulatory receptor CD28 in comparison to their circulating memory counterparts. Accordingly, PD-1 inhibition improved proliferation of circulating tumor-specific CD8+ T cells and reversed functional exhaustion of specific T cells at tumor sites. In agreement with their tumor specificity, high infiltration of tumors by exhausted cells was predictive of response to therapy and survival in ICB-treated head and neck cancer patients. Our results showed that PD-1 blockade-mediated proliferation/reinvigoration of circulating memory T cells and local reversion of exhaustion occur concurrently to control tumors. Copyright ©2020, American Association for Cancer Research.Mizagliflozin concentration