Adenoviral-based vaccine promotes neoantigen-specific CD8+ T cell stemness and tumor rejection.

Upon chronic antigen exposure, CD8+ T cells become exhausted, acquiring a dysfunctional state correlated with the inability to control infection or tumor progression. In contrast, stem-like CD8+ T progenitors maintain the ability to promote and sustain effective immunity. Adenovirus (Ad)-vectored vaccines encoding tumor neoantigens have been shown to eradicate large tumors when combined with anti-programmed cell death protein 1 (αPD-1) in murine models; however, the mechanisms and translational potential have not yet been elucidated. Here, we show that gorilla Ad vaccine targeting tumor neoepitopes enhances responses to αPD-1 therapy by improving immunogenicity and antitumor efficacy. Single-cell RNA sequencing demonstrated that the combination of Ad vaccine and αPD-1 increased the number of murine polyfunctional neoantigen-specific CD8+ T cells over αPD-1 monotherapy, with an accumulation of Tcf1+ stem-like progenitors in draining lymph nodes and effector CD8+ T cells in tumors. Combined T cell receptor (TCR) sequencing analysis highlighted a broader spectrum of neoantigen-specific CD8+ T cells upon vaccination compared to αPD-1 monotherapy. The translational relevance of these data is supported by results obtained in the first 12 patients with metastatic deficient mismatch repair (dMMR) tumors vaccinated with an Ad vaccine encoding shared neoantigens. Expansion and diversification of TCRs were observed in post-treatment biopsies of patients with clinical response, as well as an increase in tumor-infiltrating T cells with an effector memory signature. These findings indicate a promising mechanism to overcome resistance to PD-1 blockade by promoting immunogenicity and broadening the spectrum and magnitude of neoantigen-specific T cells infiltrating tumors.

Active surveillance of chemotherapy-related symptom burden in ambulatory cancer patients via the implementation of electronic patient-reported outcomes and sensor-enabled vital signs capture: protocol for a decentralised feasibility pilot study.

INTRODUCTION: Remote patient monitoring (RPM) has emerged as a potential avenue for optimising the management of symptoms in patients undergoing chemotherapy. However, RPM is a complex, multilevel intervention with technology, workflow, contextual and patient experience components. The purpose of this pilot study is to determine the feasibility of RPM protocol implementation with respect to decentralised recruitment, patient retention, adherence to reporting recommendations, RPM platform usability and patient experience in ambulatory cancer patients at high risk for chemotherapy-related symptoms. METHODS AND ANALYSIS: This protocol describes a single-arm decentralised feasibility pilot study of technology-enhanced outpatient symptom management system in patients with gastrointestinal and thoracic cancer receiving chemotherapy and cancer care at a single site (MD Anderson Cancer Center, Houston Texas). An anticipated total of 25 patients will be recruited prior to the initiation of chemotherapy and provided with a set of validated questionnaires at enrollment and after our 1-month feasibility pilot trial period. Our intervention entails the self-reporting of symptoms and vital signs via a HIPAA-compliant, secure tablet interface that also enables (1) the provision of self-care materials to patients, (2) generation of threshold alerts to a dedicated call-centre and (3) videoconferencing. Vital sign information (heart rate, blood pressure, pulse, oxygen saturation, weight and temperature) will be captured via Bluetooth-enabled biometric monitoring devices which are integrated with the tablet interface. Protocolised triage and management of symptoms will occur in response to the alerts. Feasibility and acceptability metrics will characterise our recruitment process, protocol adherence, patient retention and usability of the RPM platform. We will also document the perceived effectiveness of our intervention by patients. ETHICS AND DISSEMINATION: This study has been granted approval by the institutional review board of MD Anderson Cancer Center. We anticipate dissemination of our pilot and subsequent effectiveness trial results via presentations at national conferences and peer-reviewed publications in the relevant medical journals. Our results will also be made available to cancer survivors, their caregivers and hospital administration. TRIAL REGISTRATION NUMBER: NCI202107464.

Underreporting of race/ethnicity in COVID-19 research.

OBJECTIVES: Although racial/ethnic disparities in healthcare have long been recognized, recent discourse around structural racism will hopefully lead to improved transparency surrounding these issues. Despite the disproportionate impact of COVID-19 on racial/ethnic minorities, the extent and reliability of race reporting in COVID research is unclear. METHODS: COVID-19 research published in three top medical journals during the first wave of the COVID-19 pandemic was reviewed and assessed for race reporting and proportional representation. RESULTS: Of the 95 manuscripts that were identified, 56 reporting on 252,262 patients met eligibility. Thirty-five (62.5%) did not report race distribution and 15 (26.7%) did not report ethnicity. There was no difference based on journal (P = 0.87), study sponsor (P = 0.41), whether the study was retrospective or prospective (P = 0.33), or observational vs interventional (P = 0.11). Studies with ≥250 patients were more likely to report on race (OR 4.01, 95% CI: 1.12-14.37, P = 0.027), and North American (USA and Canada) studies were more likely than European studies (OR 7.88, 95% CI: 1.73-37.68, P = 0.006) to report on race. COVID-19 research mirrored USA COVID-19 racial incidence; however, both showed higher distribution of COVID-19 infection among Blacks and a smaller proportion of Whites compared to the USA population. This suggests that research is broadly representing infection rates and that social determinants of health are impacting racial distribution of infection. CONCLUSIONS: Despite increasing awareness of racial disparities and inequity, COVID-19 research during the first wave of the pandemic lacked appropriate racial/ethnicity reporting. However, research mirrored COVID-19 incidence in the USA, with an increased burden of infection among Black individuals.