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Abstract: Primary effusion lymphoma (PEL) is a rare and aggressive B-cell lymphoma typically associated with human herpesvirus 8 (HHV-8) and Epstein-Barr virus infections. It classically presents as a malignant effusion in body cavities, but rarely presents with an extracavitary variant characterized by solid tumors in lymph nodes or extranodal sites such as the gastrointestinal tract, skin, lungs, and nervous system. This case report describes an unusual presentation of primary cutaneous extracavitary PEL in an HIV-positive patient that has only been reported in 8 cases previously. The patient presented with a skin nodule in the right supraclavicular area. Histopathologic examination showed a malignant infiltrate in the dermis composed of sheets of plasmablasts. The immunophenotype of the cells shows the characteristic coinfection with HHV-8 and Epstein-Barr virus. The case presented herein contributes to expand the reported literature on primary cutaneous extracavitary PEL and performs a comprehensive review of this entity, which most dermatopathologists are unfamiliar with., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Malignant tenosynovial giant cell tumor (MTGCT) is a rare and aggressive variant of tenosynovial giant cell tumors, with fewer than 60 reported cases. Although typically localized to joints and soft tissues, cutaneous presentations of MTGCT are exceedingly rare, with only a handful of documented cases involving direct dermal invasion. Here we report the case of an 88-year-old man with a history of nonmelanoma skin cancers who presented with a friable, ulcerated 2.5 cm nodule on the midchest. The lesion, present for approximately 1 month, was excised and found to be a malignant TGCT. Histopathology revealed a neoplasm with multinucleated giant cells and malignant features such as numerous and atypical mitotic figures, necrosis, and severe cellular pleomorphism. Immunohistochemistry showed positivity for CD45 and CD68, with weak partial expression of smooth muscle actin, and negative for CD34, P40, SOX10, pancytokeratin, CD163, CD1a, S100, and Melan-A, confirming the diagnosis. The patient underwent complete surgical excision. This case highlights a rare presentation of MTGCT with direct cutaneous involvement, adding to the sparse literature on this malignancy. Early recognition and accurate diagnosis of such unusual presentations are crucial because of the tumor's aggressive potential., Competing Interests: A. Mehta: SkinCheck (start-up chief of staff); A. A. Gru: Seattle Genetics (consultant); Innate Pharma (coinvestigator); StemLine Therapeutics (consultant, investigator); Kyowa Kyrin (consultant, speaker); Cerba Research (investigator); CRISPR Therapeutics (coinvestigator). The remaining author declares no conflicts of interest., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Melanoma, an aggressive skin cancer, presents significant therapeutic challenges. Consequently, innovative treatment strategies beyond conventional chemotherapy, radiation, and surgery are actively explored. This review discusses the evolution of immunotherapy in advanced melanoma, highlighting PD-1/PD-L1 inhibitors, mRNA vaccines, Talimogene Laherparepvec (T-VEC), and tumor-infiltrating lymphocyte (TIL) therapies. PD-1/PD-L1 inhibitors such as pembrolizumab and nivolumab block immune checkpoints, promoting T-cell cytotoxic activity and improving overall survival in patients with advanced melanoma. T-VEC, a modified oncolytic herpes virus, promotes a systemic anti-tumor response while simultaneously lysing malignant cells. mRNA vaccines, such as Moderna's mRNA-4157/V940, take advantage of malignant-cell-specific neoantigens to amplify the adaptive immune response while protecting healthy tissue. TIL therapy is a form of therapy involving ex vivo expansion and reinfusion of the patient's tumor-specific lymphocytes and has been shown to provide durable tumor control. While these therapies have demonstrated promising clinical outcomes, challenges such as tumor resistance, high financial burden, and limited accessibility pose challenges to their widespread use. This review explores combination therapies such as PD-L1 inhibitors with mRNA vaccines, or TIL therapy, which aim to enhance treatment through synergistic approaches. Further research is required to optimize these combinations, address barriers preventing their use, and control adverse events.

Abstract: Interdigitating dendritic cell sarcoma is a rare, aggressive hematological malignancy primarily originating in lymph nodes, with only 10 reported cases presenting in the skin (primary cutaneous interdigitating dendritic cell sarcoma). Past presentations showed erythematous nodules on the proximal extremities, back, or face. Morphologically, these neoplasms are similar to melanomas and other dendritic cell (DC) tumors, making their diagnosis difficult. Here, we present 1 case of primary cutaneous interdigitating dendritic cell sarcomas and another 1 of malignant indeterminate dendritic cell tumor (indeterminate DC sarcoma). The first case is an 83-year-old man who presented with recent ulceration and bleeding of an asymptomatic, slow growing lesion on his right thigh with biopsy revealing a large, well-circumscribed polypoid spindle cell tumor in the dermis with atypical cells with vesicular nuclei in a lymphoplasmacytic background and immunohistochemistry positivity for CD45, CD68, S100, and Cyclin D1. The second case is a 74-year-old man who presented with a progressively darkening and enlarging abdominal skin lesion with biopsy revealing a diffuse infiltrate of atypical poorly differentiated pleomorphic nuclear cells and immunohistochemistry positivity for S100, CD1a, CD56, CD43, cyclin D1, CD31, CD4, and BRAF V600E. Our findings contribute to expand the reported literature on primary cutaneous DC sarcomas., Competing Interests: A. A. Gru: Seattle Genetics (Consultant); Innate Pharma (Co-investigator); StemLine Therapeutics (Consultant, Investigator); Kyowa Kyrin (Consultant, Speaker); Cerba Research (Investigator); CRISPR Therapeutics (Co-investigator). The remaining authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Respiratory virus infections in humans cause a broad-spectrum of diseases that result in substantial morbidity and mortality annually worldwide. To reduce the global burden of respiratory viral diseases, preventative and therapeutic interventions that are accessible and effective are urgently needed, especially in countries that are disproportionately affected. Repurposing generic medicine has the potential to bring new treatments for infectious diseases to patients efficiently and equitably. In this study, we found that intranasal delivery of neomycin, a generic aminoglycoside antibiotic, induces the expression of interferon-stimulated genes (ISGs) in the nasal mucosa that is independent of the commensal microbiota. Prophylactic or therapeutic administration of neomycin provided significant protection against upper respiratory infection and lethal disease in a mouse model of COVID-19. Furthermore, neomycin treatment protected Mx1 congenic mice from upper and lower respiratory infections with a highly virulent strain of influenza A virus. In Syrian hamsters, neomycin treatment potently mitigated contact transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In healthy humans, intranasal application of neomycin-containing Neosporin ointment was well tolerated and effective at inducing ISG expression in the nose in a subset of participants. These findings suggest that neomycin has the potential to be harnessed as a host-directed antiviral strategy for the prevention and treatment of respiratory viral infections., Competing Interests: Competing interests statement:A.I. co-founded and consults for RIGImmune, Xanadu Bio and PanV, consults for Paratus Sciences, InvisiShield Technologies, and is a member of the Board of Directors of Roche Holding Ltd.

Chiral analysis has become a crucial step in studying the stereospecific synthesis of Active Pharmaceutical Ingredients (APIs). Both Vibrational Circular Dichroism (VCD) and Molecular Rotational Resonance (MRR) spectroscopy are capable of determining absolute configurations (ACs) via comparison of experimental and calculated data. In this regard, each technique has its own caveats. In VCD analysis, accurate prediction of the normal modes as well as rigorous conformational searches of both the analyte and potential (self-)aggregation products are required to optimally match experimental spectra. In MRR analysis, chiral species are resolved through complexation with a chiral tag to prepare spectrally distinct diastereomeric complexes. Although individual complex isomers can be distinguished, spectral assignments need to be matched to unique isomer geometries for unambiguous AC assignment. In this work, the ACs of two highly fluorinated carboxylic acids were successfully assigned using VCD and MRR spectroscopy. In the VCD analysis, the M06-2X functional was demonstrated to be superior to B3LYP and B3LYP-GD3 in accurately predicting the C-F normal modes and both monomeric and dimeric spectral contributions were observed. In a similar analysis with broadband MRR, most experimentally identified geometries had more than one possible computational match. Nevertheless, careful consideration of the chiral tag, as well as additional isomer assignments, resulted in successful assignment of the AC. This comparative study demonstrates the power of contemporary VCD analysis and the unique contributions of MRR to the analytical toolbox., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Long term sick leave (SL) is increasing in Europe, several countries have legislative initiatives to reduce long-term absenteeism., Objective: We evaluated the impact of a legally defined return-to-work (RTW) trajectory on the RTW of employees on sick leave in Belgium., Methods: This was a retrospective register-based cohort study of employees (n = 1416) who followed an RTW trajectory in 2017. We linked workers' data from a prevention service with social security data. By multinomial logistic regression, we analysed which characteristics predicted the RTW with the same or another employer., Results: One year after their RTW trajectory, 69.2% of the 1416 employees did not RTW; 10.7% returned to work with the same employer and 20.1% with a new employer. Duration of SL was an important predictor for the RTW with both the same employer and another employer. The odds of RTW were lower when the SL duration was >  6 months compared to <  6 months. Marital status, organization-size, and the occupational physician decision had a significant impact on the RTW with the same employer. Age and who initiated the RTW-trajectory were important predictors on the RTW with another employer., Conclusions: Overall, 30.8% of employees returned to work after their RTW trajectory. A one-size-fits-all approach is not recommended. A stepped approach with an early, informal start of the RTW process is advised. When employees or employers fail to initiate the RTW on their own, a legally defined RTW trajectory could be useful. In particular, RTW with another employer seemed a positive effect of the RTW-trajectory.

The ability of immune cells to directly interact with transformed cells is an essential component of immune surveillance and critical for optimal tissue function. The tumor-immune interactome (the collective cellular interactions between oncogenic cells and immune cells) is distinct and varied based on the tissue location and immunogenicity of tumor subtypes. However, comprehensive landscape and the consequences of tumor-interacting immune cells in the tumor microenvironment are not well understood. Current tools are limited in their ability to identify and record interactors in vivo or be utilized for downstream analysis. Here, we describe the development and validation of a technology leveraging synthetic Notch receptors reporting physical tumor cell-immune cell contact in vivo in order to decipher the tumor-immune interactome. We call this approach, Tumor-Immune Interactome Non-biased Discovery Retroviral Reporter or TIINDRR. Using TIINDRR, we identify the tumor-immune interactomes that define immunological refractory and sensitive tumors and how different immunotherapies alter these interactions. Thus, TIINDRR provides a flexible and versatile tool for studying in-vivo tumor-immune cell interactions, aiding in the identification of biologically relevant information needed for the rational design of immune-based therapies.

The progression of transformed primary tumors to metastatic colonization is a lethal determinant of disease outcome. Although circulating adaptive and innate lymphocyte effector responses are required for effective antimetastatic immunity, whether tissue-resident immune circuits confer initial immunity at sites of metastatic dissemination remains ill defined. Here we examine the nature of local immune cell responses during early metastatic seeding in the lung using intracardiac injection to mimic monodispersed metastatic spread. Using syngeneic murine melanoma and colon cancer models, we demonstrate that lung-resident conventional type 2 dendritic cells (DC2) orchestrate a local immune circuit to confer host antimetastatic immunity. Tissue-specific ablation of lung DC2, and not peripheral DC populations, led to increased metastatic burden in the presence of an intact T cell and NK cell compartment. We demonstrate that DC nucleic acid sensing and transcription factors IRF3 and IRF7 signaling are required for early metastatic control and that DC2 serve as a robust source of proinflammatory cytokines in the lung. Critically, DC2 direct the local production of IFN-γ by lung-resident NK cells, which limits the initial metastatic burden. Collectively, our results highlight, to our knowledge, a novel DC2-NK cell axis that colocalizes around pioneering metastatic cells to orchestrate an early innate immune response program to limit initial metastatic burden in the lung., (Copyright © 2023 The Authors.)

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has highlighted the need for vaccines that not only prevent disease but also prevent transmission. Parenteral vaccines induce robust systemic immunity but poor immunity at the respiratory mucosa. We developed a vaccine strategy that we call "prime and spike," which leverages existing immunity generated by primary vaccination (prime) to elicit mucosal immune memory within the respiratory tract by using unadjuvanted intranasal spike boosters (spike). We show that prime and spike induces robust resident memory B and T cell responses, induces immunoglobulin A at the respiratory mucosa, boosts systemic immunity, and completely protects mice with partial immunity from lethal SARS-CoV-2 infection. Using divergent spike proteins, prime and spike enables the induction of cross-reactive immunity against sarbecoviruses.

Objective: This study will synthesize the available evidence on the prevalence and incidence of chemotherapy-induced taste alterations in adult cancer patients., Introduction: Taste and smell alterations in cancer patients due to chemotherapy affect patients' quality of life and can cause malnutrition. Recent knowledge about the incidence and prevalence of chemotherapy-induced taste alterations may enable tailored food interventions for this specific population. Describing variations in taste changes in subgroups of chemotherapy is important to inform taste steering interventions., Inclusion Criteria: The review will consider studies that include adult cancer patients who are receiving or have received chemotherapy as a treatment for an oncologic issue. It will include studies that investigate the prevalence and incidence of chemotherapy-induced taste alterations that have been assessed objectively or subjectively by patient-reported outcomes., Methods: A systematic search will be performed of the following databases: MEDLINE (PubMed), CINAHL (Ovid), Embase, and OpenSIGLE. Analytical, observational, and cross-sectional studies will be considered. All studies will undergo critical appraisal, data extraction, and synthesis. Data will be extracted using the JBI standardized data extraction tool for prevalence and incidence. Type and frequency of treatment and cytostatic agent will be extracted. The population will be described by age and gender. In addition, study methods and proportions of interest to the review question will be extracted. Pooled prevalence estimates will be calculated using a random effects model., Systematic Review: PROSPERO CRD42020136706., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 JBI.)

Purpose: The purpose of this report was to describe a case with paracentral acute middle maculopathy after oral intake of sumatriptan., Methods: Case presentation., Results: One patient showed typical findings on fundoscopic examination and optical coherence tomography consistent with paracentral acute middle maculopathy following oral intake of sumatriptan., Conclusion: Sumatriptan may be a trigger for paracentral acute middle maculopathy.

Memory T cells can be generated and remain long-term in different tissues following infection or immunization. Tissue-resident memory T (T RM ) cells are a unique group of memory T cells that form and persist mainly in peripheral non-lymphoid organs. Unlike effector or central memory T (T EM or T CM ) cells, T RM cells do not circulate to the blood but can provide a rapid and robust local response to re-infection. Recently, a large body of clinical studies has shown that CD103 + CD8 + T RM -like cells also exist intratumorally and strongly correlate with favorable prognosis in cancer patients. Cancer vaccine-induced CD103 + CD8 + T RM cells have been reported to suppress tumor growth in mouse models. This suggests that CD8 + T RM -like cells play a crucial role in cancer immunosurveillance and immunotherapy. In this review, we focus on the features and cytotoxic mechanisms of CD8 + T RM -like cells in multiple solid tumors and discuss their potential implications for cancer immunotherapy. We believe a better understanding of the generation, function, and longevity of CD8 + T RM -like cells in the tumor microenvironment will provide new insights for cancer immunotherapies., (Copyright © 2020 Elsevier Ltd. All rights reserved.)