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Deciphering immune recognition is critical for understanding a broad range of diseases and for the development of effective vaccines and immunotherapies. Efforts to do so are limited by a lack of technologies capable of simultaneously capturing the complexity of adaptive immunoreceptor repertoires and the landscape of potential antigens. To address this, we present receptor–antigen pairing by targeted retroviruses, which combines viral pseudotyping and molecular engineering approaches to enable one-pot library-on-library interaction screens by displaying antigens on the surface of lentiviruses and encoding their identity in the viral genome. Antigen-specific viral infection of cell lines expressing human T or B cell receptors allows readout of both antigen and receptor identities via single-cell sequencing. The resulting system is modular, scalable and compatible with any cell type. These techniques provide a suite of tools for targeted viral entry, molecular engineering and interaction screens with broad potential applications. RAPTR, a lentivirus surface display-based library-on-library screening method to decipher antigen and immunoreceptor identities

Loading of MHC-I molecules with peptide by the catalytic chaperone tapasin in the peptide loading complex plays a critical role in antigen presentation and immune recognition. Mechanistic insight has been hampered by the lack of detailed structural information concerning tapasin–MHC-I. We present here crystal structures of human tapasin complexed with the MHC-I molecule HLA-B*44:05, and with each of two anti-tapasin antibodies. The tapasin-stabilized peptide-receptive state of HLA-B*44:05 is characterized by distortion of the peptide binding groove and destabilization of the β 2 -microglobulin interaction, leading to release of peptide. Movements of the membrane proximal Ig-like domains of tapasin, HLA-B*44:05, and β 2 -microglobulin accompany the transition to a peptide-receptive state. Together this ensemble of crystal structures provides insights into a distinct mechanism of tapasin-mediated peptide exchange. The catalytic chaperone tapasin assists peptide loading onto MHC-I molecules for antigen presentation and immune recognition. Here, the authors present crystal structures that provide insights into the molecular mechanism of tapasin-mediated peptide exchange.

IntroductionCutaneous T cell lymphoma (CTCL) is a group of non-Hodgkin lymphomas that primarily affects the skin and can mimic inflammatory dermatoses. Unlike many skin diseases, CTCL can lead to disabling symptoms, and advanced CTCL can even be fatal. Early studies investigating health-related quality of life (HRQOL) in patients with mycosis fungoides (MF) and Sézary syndrome (SS), common subtypes of CTCL, demonstrated significant impairment across numerous domains. The aim of this current study is to develop a core domain set (CDS) to identify the essential aspects of MF/SS that influence HRQOL that should be measured in therapeutic clinical trials. In the future, this set of core concepts will be used to identify the best patient- reported outcome measure(s) (PROM) for HRQOL for MF/SS clinical research.Methods and analysisMultiple strategies will be used to generate candidate concepts: systematic review of the literature, qualitative study and a survey study of healthcare providers. A Delphi consensus process including a comprehensive group of stakeholders (patients, caregivers/care partners, a multidisciplinary group of healthcare professionals, patient advocacy groups, pharmaceutical industry representatives, methodologists and government agencies) will be used to achieve consensus. Statistical corrections for multiple significance testing and false positive findings will be undertaken.Ethics and disseminationThe study was submitted for and received institutional review board approval at the University of Washington (IRB# STUDY00018890 and STUDY00019407). Informed consent will be obtained from all participants where necessary. We will disseminate our findings through peer-reviewed, open access publications and presentations at national/international conferences. We will provide a plain language summary in lay terms for patients and families to patient advocacy groups for distribution to their network.Registration detailsThe protocol is registered in the Core Outcome Measures in Effectiveness Trials (COMET) database.

Background There is no consensus on how best to assess the impact of living with mycosis fungoides (MF)/Sézary syndrome (SS) on a patient's quality of life. Objectives To identify all potential concepts that describe disease severity or contribute to health‐related quality of life (HRQOL) from patients with MF/SS and their care partners. Methods A systemic literature review of articles and meeting s published between 2000 and 2022 was conducted. Inclusion criteria were any study that included MF/SS patients or care partners and reported any concept that patients or care partners could use to characterize any aspect of MF/SS. Thematic analysis was completed using NVIVO. Results One hundred and three articles/s met inclusion criteria. Within these studies, 30 existing instruments were utilized. Concepts within these existing instruments fell into the following health component categories: Physical‐functional well‐being (PF; 50.4%), mental health/emotional well‐being (MHE; 26.6%), social well‐being (S; 18.3%) or other (O; 4.7%). The most frequently measured concepts by existing instruments were physical mobility (7.5%), itching (7.2%), pain (7.0%) and fatigue (5.2%). One study conducted content validity analysis for an included instrument. Distinct concepts were identified from qualitative studies and novel instruments, and included hair loss, nail changes, cracking/fissuring of the skin, inability to regulate temperature, difficulty with wound dressings, skin infection, skin oozing/weeping/bleeding, pigmentary changes, treatment burden and treatment satisfaction, and care partners' specific concepts. One study conducted content validity analysis for an included instrument. Conclusions Numerous PROMs have been used to assess HRQOL for patients with MF/SS, with very little content validity analysis. Several concepts identified from qualitative studies and newly developed or piloted instruments are not represented in existing PROMs. Future efforts will include prioritizing candidate core concepts by stakeholders to develop a core domain set that captures the most relevant aspects of MF/SS that impact HRQOL. Summary The purpose of this study was to identify all potential concepts related to disease severity or contribute to health‐related quality of life (HRQOL) elicited from patients with mycosis fungoides/Sézary syndrome (MF/SS) and their care partners. We provide a comprehensive list of concepts that patients and caregivers use to describe disease severity and HRQOL. We identify gaps in instruments commonly used to assess HRQOL for patients with MF/SS. Numerous different measures have been used to assess HRQOL for patients with MF/SS, with little content validity analysis. An all‐inclusive summary of candidate concepts is a critical first step to enable the development of a core domain set that captures the most relevant aspects of MF/SS that impact HRQOL. There is no consensus on how best to assess the impact of living with mycosis fungoides (MF)/Sézary Syndrome (SS). We conducted a systemic literature review of any study that included MF/SS patients or care partners and reported any concept this group could use to characterize any aspect of MF/SS. Thematic analysis was completed using NVIVO. 103 studies were included that utilized 30 existing instruments and several novel concepts. Future efforts include prioritizing candidate concepts for a core domain set. Trial Registration PROSPERO number: CRD42024511024.

Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the efficacy of mogamulizumab, a novel monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with previously treated cutaneous T-cell lymphoma. In this open-label, international, phase 3, randomised controlled trial, we recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia. Eligible patients were aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function. Patients were randomly assigned (1:1) using an interactive voice web response system to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB–II vs III–IV). Since this study was open label, patients and investigators were not masked to treatment assignment. The primary endpoint was progression-free survival by investigator assessment in the intention-to-treat population. Patients who received one or more doses of study drug were included in the safety analyses. This study is ongoing, and enrolment is complete. This trial was registered with ClinicalTrials.gov, number NCT01728805. Between Dec 12, 2012, and Jan 29, 2016, 372 eligible patients were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186), comprising the intention-to-treat population. Two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment; thus, 370 patients were included in the safety population. Mogamulizumab therapy resulted in superior investigator-assessed progression-free survival compared with vorinostat therapy (median 7·7 months [95% CI 5·7–10·3] in the mogamulizumab group vs 3·1 months [2·9–4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41–0·69; stratified log-rank p<0·0001). Grade 3–4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group; and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related. Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma. Kyowa Kirin.

•A high percentage of patients with cutaneous T-cell lymphoma use integrative medicine for their disease.•Nearly half of our patients reported using integrative medicine specifically to treat their lymphoma.•The most common forms of integrative medicine therapies in our cohort were vitamins/minerals, prayer/meditation, and diet.•Health-related quality of life was worse among patients who reported integrative medicine use. To characterize patterns of integrative medicine (IM) use and health-related quality of life (HRQoL) in patients with cutaneous T-cell lymphoma (CTCL). Cross-sectional, online survey, created in conjunction with the Cutaneous Lymphoma Foundation (CLF). A link to the online survey was posted on the CLF Facebook page and emailed to the CLF listserv; 372 survey responses were received. The study outcomes were IM use, cancer symptoms, and HRQoL measured via the Skindex-16 and Functional Assessment of Cancer Therapy-General (FACT-G). A total of 292 patient responses (66 % female, median age 59y) were included in analysis. 87 % had mycosis fungoides and 12 % had Sézary syndrome. A majority (59 %) of patients reported using IM for their CTCL, with 48 % using IM to treat their disease and 47 % using IM to manage their symptoms. The most commonly used IM were vitamins/minerals (32 %), prayer/meditation (26 %), diet (24 %), and exercise/yoga (22 %). Higher itch scores were reported by patients using IM compared to non-users (31 (IQR 10–62) and 18 (IQR 3–46) respectively; p = 0.002). HRQoL was worse among patients who reported IM use; median Skindex-16 scores were 54 (IQR 28–72) among IM users compared to 33 (IQR 19–57) for non-IM users (p < 0.001). IM use is common among patients with CTCL, particularly those with worse itching and worse HRQoL. IM interventions require further study given use by CTCL patients to treat disease and ameliorate symptoms.

Parapsoriasis is an uncommon inflammatory skin disease characterized by chronic patches that may be resistant to therapy. It was primarily introduced and classified 120 years ago, and the original classification incorporated parapsoriasis and pityriasis lichenoides under the umbrella term parapsoriasis. After a major change in classification, parapsoriasis now exclusively refers to small plaque parapsoriasis (SPP) and large plaque parapsoriasis (LPP). However, debates still frequently occur regarding various nomenclatures and classifications used by different authors. Moreover, parapsoriasis may progress to overt cutaneous lymphoma, most commonly mycosis fungoides (MF), and it is very difficult to distinguish these two conditions despite modern histologic and molecular testing techniques. As parapsoriasis is a rare disease, there is a lack of studies and clinical guidelines to assist physicians in clinical practice. In our comprehensive review, we review several aspects of parapsoriasis, from the history of nomenclature and classification, clinical characteristics, immunohistopathology, and advanced molecular techniques for the diagnosis of this condition, to the most current treatments. We also propose a scheme for distinguishing parapsoriasis from early-stage MF in this review.

Background Chlormethine/mechlorethamine gel is a skin-directed therapy for patients with mycosis fungoides cutaneous T-cell lymphoma. Currently, real-world data on chlormethine gel are lacking. Objective Our objective was to analyze the effect of chlormethine gel in combination with other therapies on efficacy, safety, and health-related quality of life in a real-world setting. Methods This prospective, observational study enrolled adult patients actively using chlormethine gel. Patients were monitored for up to 2 years during standard-of-care clinic visits. No specific visit schedules or clinical assessments, with the exception of patient-completed questionnaires, were mandated because of the expected variability in practice patterns. The primary efficacy endpoint was the proportion of patients with stage IA–IB disease receiving chlormethine + topical corticosteroids + other with ≥ 50% decrease in body surface area from baseline to 12 months. Response was assessed at each visit using by-time analysis, which investigates the trend to treatment response and allows assessment of response over time. Health-related quality of life was assessed with the Skindex-29 questionnaire. Results In total, 298 patients were monitored. At 12 months post-treatment initiation, 44.4% (chlormethine + topical corticosteroids + other) and 45.1% (patients receiving chlormethine + other treatment) of efficacy-evaluable patients were responders. By-time analysis demonstrated that peak response occurred (chlormethine + other; 66.7%) at 18 months. There was a significant correlation between responder status and lower post-baseline Skindex-29 scores. Conclusions This real-world study confirmed that chlormethine gel is an important therapeutic option for patients with mycosis fungoides and contributes to reducing the severity of skin lesions and improving health-related quality of life. Infographic

Mycosis fungoides (MF), the most common form of primary cutaneous T-cell lymphoma, is a disease typically with an indolent course that is initially characterized by localized patches and plaques. In the early stages of the disease, treatment involves skin-directed therapies (SDTs) such as topical corticosteroids and retinoids. Chlormethine gel (also known as mechlorethamine) was the first SDT purposely developed to treat MF and is currently endorsed by international guidelines for the treatment of adult patients with MF as a first-line therapy. While chlormethine is an efficacious therapy, its usage may be complicated by the development of cutaneous reactions at the sites of application. Herein, we discuss the supportive guidelines for MF and the suitability of chlormethine as a therapeutic option in patients with MF. In addition, we present real-world experience on the use of chlormethine gel from clinics in the USA, Israel, and France with the aim of demonstrating the efficacy of chlormethine gel in routine clinical practice and outlining strategies that are being used to manage emergent cutaneous reactions. Infographic