Pre-existing skin-resident CD8 and gd T cell circuits mediate immune response in Merkel cell carcinoma and predict immunotherapy efficacy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer with a ~50% response rate to immune checkpoint blockade (ICB) therapy. To identify predictive biomarkers, we integrated bulk and single-cell RNA-seq with spatial transcriptomics from a cohort of 186 samples from 116 patients, including bulk RNA-seq from 14 matched pairs pre- and post-ICB. In non-responders, tumors show evidence of increased tumor proliferation, neuronal stem cell markers, and IL-1. Responders have increased type I/II interferons and pre-existing tissue resident (Trm) CD8 or Vd1 gd T cells that functionally converge with overlapping antigen-specific transcriptional programs and clonal expansion of public TCRs. Spatial transcriptomics demonstrated co-localization of T cells with B and dendritic cells, which supply chemokines and co-stimulation. Lastly, ICB significantly increased clonal expansion or recruitment of Trm and Vd1 cells in tumors specifically in responders, underscoring their therapeutic importance. These data identify potential clinically actionable biomarkers and therapeutic targets for MCC.

A rare sweat gland tumor in an ovarian teratoma: Spiradenocylindroma case report.

Background: Spiradenocylindroma is a benign tumor of skin adnexal origin with overlapping features of two distinct neoplasms: spiradenoma and cylindroma. This cutaneous tumor typically presents on the head and neck and extracutaneous presentations are uncommon. The presentation described below involves a spiradenocylindroma within a mature ovarian teratoma is very rare. Aim: The aim of this article is to portray the diagnostic process of this unusual spiradenocylindroma presentation. Case presentation: A 65 year-old female with a left adnexal mass underwent ultrasonography and magnetic resonance imaging (MRI) which showed a left ovarian multiseptated lesion, with mural calcifications and projections into the mass. Excisional surgery was performed and histopathological examination revealed a spiradenocylindroma. Conclusion: Spiradenocylindroma is rare, hard to identify, and often misdiagnosed. Our study described the process of diagnosis and depicts the rare presentation of this lesion arising within a mature teratoma.

Melanoma in Pediatric and Young Adult Patients.

PURPOSE OF REVIEW: Melanoma in younger individuals has different clinical presentations, histologic characteristics and prognosis from older patients. This review summarizes key differences and important new insights into pediatric and young adult melanoma, as well as recent evolutions in treatment. RECENT FINDINGS: Molecular techniques have improved the classification of melanocytic neoplasms, and are especially useful in the workup of the diagnostically challenging lesions frequent in this age group. Molecular evaluation highlights differences between melanoma and atypical lesions with Spitz-like morphology, and should routinely be incorporated for diagnosing and classifying Spitzoid melanocytic to guide prognostication and treatment. Once diagnosed, the management of bona fide melanoma in children and young adults is largely similar to older patients, while the optimal management of lesions such as atypical Spitz tumors remains uncertain. Increased awareness of the presentation and diagnostic characteristics of melanoma in young individuals will allow earlier detection, and improved diagnostic techniques will allow optimum management without over- or under-treatment.

The Impact of Next-generation Sequencing on Interobserver Agreement and Diagnostic Accuracy of Desmoplastic Melanocytic Neoplasms.

Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs). In this study, 20 expert melanoma pathologists rendered a diagnosis on 47 DMNs based on hematoxylin and eosin sections with demographic information. After submitting their diagnosis, the experts were given the same cases, but this time with comprehensive genomic sequencing results, and asked to render a diagnosis again. Identification of desmoplastic melanoma (DM) improved by 7%, and this difference was statistically significant ( P <0.05). In addition, among the 15 melanoma cases, in the pregenomic assessment, only 12 were favored to be DM by the experts, while after genomics, this improved to 14 of the cases being favored to be DM. In fact, some cases resulting in metastatic disease had a substantial increase in the number of experts recognizing them as DM after genomics. The impact of the genomic findings was less dramatic among benign and intermediate-grade desmoplastic tumors (BIDTs). Interobserver agreement also improved, with the Fleiss multirater Kappa being 0.36 before genomics to 0.4 after genomics. NGS has the potential to improve diagnostic accuracy in the assessment of desmoplastic melanocytic tumors. The degree of improvement will be most substantial among pathologists with some background and experience in bioinformatics and melanoma genetics.

Assessing vulnerability for future Zika virus outbreaks using seroprevalence data and environmental suitability maps.

The 2015-17 Zika virus (ZIKV) epidemic in the Americas subsided faster than expected and evolving population immunity was postulated to be the main reason. Herd immunization is suggested to occur around 60-70% seroprevalence, depending on demographic density and climate suitability. However, herd immunity was only documented for a few cities in South America, meaning a substantial portion of the population might still be vulnerable to a future Zika virus outbreak. The aim of our study was to determine the vulnerability of populations to ZIKV by comparing the environmental suitability of ZIKV transmission to the observed seroprevalence, based on published studies. Using a systematic search, we collected seroprevalence and geospatial data for 119 unique locations from 37 studies. Extracting the environmental suitability at each location and converting to a hypothetical expected seroprevalence, we were able to determine the discrepancy between observed and expected. This discrepancy is an indicator of vulnerability and divided into three categories: high risk, low risk, and very low risk. The vulnerability was used to evaluate the level of risk that each location still has for a ZIKV outbreak to occur. Of the 119 unique locations, 69 locations (58%) fell within the high risk category, 47 locations (39%) fell within the low risk category, and 3 locations (3%) fell within the very low risk category. The considerable heterogeneity between environmental suitability and seroprevalence potentially leaves a large population vulnerable to future infection. Vulnerability seems to be especially pronounced at the fringes of the environmental suitability for ZIKV (e.g. Sao Paulo, Brazil). The discrepancies between observed and expected seroprevalence raise the question: "why did the ZIKV epidemic stop with large populations unaffected?". This lack of understanding also highlights that future ZIKV outbreaks currently cannot be predicted with confidence.

Androgen drives melanoma invasiveness and metastatic spread by inducing tumorigenic fucosylation.

Melanoma incidence and mortality rates are historically higher for men than women. Although emerging studies have highlighted tumorigenic roles for the male sex hormone androgen and its receptor (AR) in melanoma, cellular and molecular mechanisms underlying these sex-associated discrepancies are poorly defined. Here, we delineate a previously undisclosed mechanism by which androgen-activated AR transcriptionally upregulates fucosyltransferase 4 (FUT4) expression, which drives melanoma invasiveness by interfering with adherens junctions (AJs). Global phosphoproteomic and fucoproteomic profiling, coupled with in vitro and in vivo functional validation, further reveal that AR-induced FUT4 fucosylates L1 cell adhesion molecule (L1CAM), which is required for FUT4-increased metastatic capacity. Tumor microarray and gene expression analyses demonstrate that AR-FUT4-L1CAM-AJs signaling correlates with pathological staging in melanoma patients. By delineating key androgen-triggered signaling that enhances metastatic aggressiveness, our findings help explain sex-associated clinical outcome disparities and highlight AR/FUT4 and its effectors as potential prognostic biomarkers and therapeutic targets in melanoma.

Differential histone acetylation and super-enhancer regulation underlie melanoma cell dedifferentiation.

Dedifferentiation or phenotype switching refers to the transition from a proliferative to an invasive cellular state. We previously identified a 122-gene epigenetic gene signature that classifies primary melanomas as low versus high risk (denoted as Epgn1 or Epgn3). We found that the transcriptomes of the Epgn1 low-risk and Epgn3 high-risk cells are similar to the proliferative and invasive cellular states, respectively. These signatures were further validated in melanoma tumor samples. Examination of the chromatin landscape revealed differential H3K27 acetylation in the Epgn1 low-risk versus Epgn3 high-risk cell lines that corroborated with a differential super-enhancer and enhancer landscape. Melanocytic lineage genes (MITF, its targets and regulators) were associated with super-enhancers in the Epgn1 low-risk state, whereas invasiveness genes were linked with Epgn3 high-risk status. We identified the ITGA3 gene as marked by a super-enhancer element in the Epgn3 invasive cells. Silencing of ITGA3 enhanced invasiveness in both in vitro and in vivo systems, suggesting it as a negative regulator of invasion. In conclusion, we define chromatin landscape changes associated with Epgn1/Epgn3 and phenotype switching during early steps of melanoma progression that regulate transcriptional reprogramming. This super-enhancer and enhancer-driven epigenetic regulatory mechanism resulting in major changes in the transcriptome could be important in future therapeutic targeting efforts.

The Brazilian COVID-19 vaccination campaign: a modelling analysis of sociodemographic factors on uptake.

OBJECTIVE: Dose shortages delayed access to COVID-19 vaccination. We aim to characterise inequality in two-dose vaccination by sociodemographic group across Brazil. DESIGN: This is a cross-sectional study. SETTING: We used data retrieved from the Brazilian Ministry of Health databases published between 17 January 2021 and 6 September 2021. METHODS: We assessed geographical inequalities in full vaccination coverage and dose by age, sex, race and socioeconomic status. We developed a Campaign Optimality Index to characterise inequality in vaccination access due to premature vaccination towards younger populations before older and vulnerable populations were fully vaccinated. Generalised linear regression was used to investigate the risk of death and hospitalisation by age group, socioeconomic status and vaccination coverage. RESULTS: Vaccination coverage is higher in the wealthier South and Southeast. Men, people of colour and low-income groups were more likely to be only partially vaccinated due to missing or delaying a second dose. Vaccination started prematurely for age groups under 50 years which may have hindered uptake in older age groups. Vaccination coverage was associated with a lower risk of death, especially in older age groups (ORs 9.7 to 29.0, 95% CI 9. 4 to 29.9). Risk of hospitalisation was greater in areas with higher vaccination rates due to higher access to care and reporting. CONCLUSIONS: Vaccination inequality persists between states, age and demographic groups despite increasing uptake. The association between hospitalisation rates and vaccination is attributed to preferential delivery to areas of greater transmission and access to healthcare.

Greenspace use during the COVID-19 pandemic: A longitudinal population mobility study in the United Kingdom.

BACKGROUND: The coronavirus pandemic greatly disrupted the lives of people. Restrictions introduced worldwide to limit the spread of infection included stay-at-home orders, closure of venues, restrictions to travel and limits to social contacts. During this time, parks and outdoor greenspaces gained prominent attention as alternative location for respite. Population mobility data offers a unique opportunity to understand the impact of the pandemic on outdoor behaviour. We examine the role of the restrictions on park use throughout the full span of the pandemic while controlling for weather and region. METHODS: This study provides a longitudinal population analysis of park visitation using Google COVID-19 Community Mobility Reports data in the UK. Daily park visitation was plotted and ANOVA analyses tested season and year effects in visitation. Then, regressions examined park visitation beyond weather (temperature and rain), according to COVID-19 restrictions, while controlling for region specificities through unit fixed effect models. RESULTS: Time series and ANOVA analyses documented the significant decrease in park visitation in the spring of 2020, the seasonal pattern in visitation, and an overall sustained and elevated use over nearly three years. Regressions confirmed park visitation increased significantly when temperature was greater and when it rained less. More visitation was also seen when there were fewer COVID-19 cases and when the stringency level of restrictions was lower. Of special interest, a significant interaction effect was found between temperature and stringency, with stringency significantly supressing the effect of higher temperature on visitation. CONCLUSIONS: COVID-19 restrictions negatively impacted park visitation on warm days. Given the general health, social, and wellbeing benefits of greenspace use, one should consider the collateral negative impact of restrictions on park visitation. When social distancing of contacts is required, the few remaining locations where it can safely occur should instead be promoted.

Grade of Primary Cutaneous Leiomyosarcoma Dictates Risk for Metastatic Spread and Disease-Specific Mortality.

BACKGROUND AND OBJECTIVES: Primary cutaneous leiomyosarcoma (cLMS), a rare, typically intradermal tumor, has previously been reported to exhibit an indolent course of disease with zero-to-low risk of local recurrence or distant metastasis. This study seeks to evaluate recurrence and survival of cLMS patients through study of its clinicopathologic and treatment characteristics. METHODS: All patients included underwent resection of primary cLMS at this institution between 2006 and 2019. A retrospective cohort study analysis of clinicopathologic characteristics, treatment, recurrence, and overall survival was performed. Data was assessed through descriptive statistics and outcome measures assessed by Cox proportional models and log-rank tests. RESULTS: Eighty-eight patients with cLMS were evaluated. The majority were men (n = 68, 77%) and Caucasian (n = 85, 97%), with median age at diagnosis of 66 years (range 20-96). 65% of tumors were located on the extremities, with a median size of 1.3 cm (range .3-15). Assessment revealed low (n = 41, 47%), intermediate (n = 29, 33%), and high (n = 18, 20%) grade tumors, demonstrating extension into subcutaneous tissue in 38/60 (60%), with 3 patients exhibiting extension into muscle (3%). All underwent resection as primary treatment with median 1 cm margins (range .5-2). With median follow-up of 27.5 months (IQR 8-51; range 1-131), no low-grade cases had recurrence or death while there was a recurrence rate of 19.1% (9/47) and death rate of 8.5% (4/47) in intermediate- to high-grade cases. CONCLUSIONS: Primary tumor resection of cLMS provides excellent local control for low-grade tumors as no low-grade cases experienced recurrence. For patients with intermediate- to high-grade tumors, there is potential for local recurrence, distant metastasis, and death, and therefore surveillance following treatment is encouraged.

A systematic review of the data, methods and environmental covariates used to map Aedes-borne arbovirus transmission risk.

BACKGROUND: Aedes (Stegomyia)-borne diseases are an expanding global threat, but gaps in surveillance make comprehensive and comparable risk assessments challenging. Geostatistical models combine data from multiple locations and use links with environmental and socioeconomic factors to make predictive risk maps. Here we systematically review past approaches to map risk for different Aedes-borne arboviruses from local to global scales, identifying differences and similarities in the data types, covariates, and modelling approaches used. METHODS: We searched on-line databases for predictive risk mapping studies for dengue, Zika, chikungunya, and yellow fever with no geographical or date restrictions. We included studies that needed to parameterise or fit their model to real-world epidemiological data and make predictions to new spatial locations of some measure of population-level risk of viral transmission (e.g. incidence, occurrence, suitability, etc.). RESULTS: We found a growing number of arbovirus risk mapping studies across all endemic regions and arboviral diseases, with a total of 176 papers published 2002-2022 with the largest increases shortly following major epidemics. Three dominant use cases emerged: (i) global maps to identify limits of transmission, estimate burden and assess impacts of future global change, (ii) regional models used to predict the spread of major epidemics between countries and (iii) national and sub-national models that use local datasets to better understand transmission dynamics to improve outbreak detection and response. Temperature and rainfall were the most popular choice of covariates (included in 50% and 40% of studies respectively) but variables such as human mobility are increasingly being included. Surprisingly, few studies (22%, 31/144) robustly tested combinations of covariates from different domains (e.g. climatic, sociodemographic, ecological, etc.) and only 49% of studies assessed predictive performance via out-of-sample validation procedures. CONCLUSIONS: Here we show that approaches to map risk for different arboviruses have diversified in response to changing use cases, epidemiology and data availability. We identify key differences in mapping approaches between different arboviral diseases, discuss future research needs and outline specific recommendations for future arbovirus mapping.

Neoantigen-specific CD4+ tumor-infiltrating lymphocytes are potent effectors identified within adoptive cell therapy products for metastatic melanoma patients.

BACKGROUND: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a promising immunotherapeutic approach for patients with advanced solid tumors. While numerous advances have been made, the contribution of neoantigen-specific CD4+T cells within TIL infusion products remains underexplored and therefore offers a significant opportunity for progress. METHODS: We analyzed infused TIL products from metastatic melanoma patients previously treated with ACT for the presence of neoantigen-specific T cells. TILs were enriched on reactivity to neoantigen peptides derived and prioritized from patient sample-directed mutanome analysis. Enriched TILs were further investigated to establish the clonal neoantigen response with respect to function, transcriptomics, and persistence following ACT. RESULTS: We discovered that neoantigen-specific TIL clones were predominantly CD4+ T cells and were present in both therapeutic responders and non-responders. CD4+ TIL demonstrated an effector T cell response with cytotoxicity toward autologous tumor in a major histocompatibility complex class II-dependent manner. These results were validated by paired TCR and single cell RNA sequencing, which elucidated transcriptomic profiles distinct to neoantigen-specific CD4+ TIL. CONCLUSIONS: Despite methods which often focus on CD8+T cells, our study supports the importance of prospective identification of neoantigen-specific CD4+ T cells within TIL products as they are a potent source of tumor-specific effectors. We further advocate for the inclusion of neoantigen-specific CD4+ TIL in future ACT protocols as a strategy to improve antitumor immunity.

The Spatial Distribution of Crimean-Congo Haemorrhagic Fever and Its Potential Vectors in Europe and Beyond.

Crimean-Congo haemorrhagic fever (CCHF) is considered to be spreading across the globe, with many countries reporting new human CCHF cases in recent decades including Georgia, Türkiye, Albania, and, most recently, Spain. We update a human CCHF distribution map produced in 2015 to include global disease occurrence records to June 2022, and we include the recent records for Europe. The predicted distributions are based on long-established spatial modelling methods and are extended to include all European countries and the surrounding areas. The map produced shows the environmental suitability for the disease, taking into account the distribution of the most important known and potential tick vectors Hyalomma marginatum and Hyalomma lusitanicum, without which the disease cannot occur. This limits the disease's predicted distribution to the Iberian Peninsula, the Mediterranean seaboard, along with Türkiye and the Caucasus, with a more patchy suitability predicted for inland Greece, the southern Balkans, and extending north to north-west France and central Europe. These updated CCHF maps can be used to identify the areas with the highest probability of disease and to therefore target areas where mitigation measures should currently be focused.

Acral melanoma: clinical advances and hope for the future.

Acral melanoma is a rare subtype of melanoma with unique histologic and biologic characteristics. Given its relative rarity compared with nonacral cutaneous melanoma, acral melanoma has been understudied and underrepresented in modern-day prospective clinical trials that have shaped the contemporary management of advanced cutaneous melanoma. Therefore, treatment principles for advanced acral melanoma are mostly derived from retrospective analyses or extrapolated from data largely based on nonacral cutaneous melanoma. Further studies are warranted to evaluate the efficacy of systemic immune and targeted molecular therapies, and to identify molecular targets for patients with advanced acral melanoma.

Wellbeing among university students during the COVID-19 pandemic: a systematic review of longitudinal studies.

OBJECTIVES: The objectives of this study were to investigate the wellbeing trajectories of university students during the COVID-19 pandemic and identify associated protective factors. Results from the study aimed to inform wellbeing-promotion strategies and crisis-response plans in university settings. STUDY DESIGN: Systematic review. METHODS: A review of articles published in English language was conducted in PubMed, PsycINFO, Scopus, Web of Science, and ERIC databases from 1 December 2019 to 15 December 2022. Longitudinal and repeated cross-sectional studies that assessed wellbeing among university students during the COVID-19 pandemic using a validated instrument were included. Article and data extraction were performed by the primary reviewer, with a random subset verified by a second reviewer. Study quality was assessed using the National Institutes of Health 'Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies'. RESULTS: Of 6651 titles screened without duplicates, 181 underwent full-text review, of which 19 were included in the current study (15 longitudinal and 4 repeated cross-sectional studies, with a total of 19,206 participants). A significant decrease in the wellbeing of university students was observed across studies during the early stages of the pandemic compared to prepandemic times; however, mixed findings were found in later phases of the pandemic, with some studies presenting an improvement in wellbeing, others no change, and two studies finding impairments. Overall, wellbeing was greater among males and was also associated with socioeconomic status, more sleep and physical activity, greater social connectedness, less alcohol use, and less social media activity. CONCLUSION: The study showed varying wellbeing trajectories across different periods of the COVID-19 pandemic. Results provide relevant information for researchers, public health professionals, and higher education institutions in charge of promoting student wellbeing and crisis preparedness. PROSPERO REGISTRATION: CRD42022383941.

Circulating tumor DNA-based molecular residual disease detection for treatment monitoring in advanced melanoma patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have substantially improved overall survival in patients with advanced melanoma; however, the lack of biomarkers to monitor treatment response and relapse remains an important clinical challenge. Thus, a reliable biomarker is needed that can risk-stratify patients for disease recurrence and predict response to treatment. METHODS: A retrospective analysis using a personalized, tumor-informed circulating tumor DNA (ctDNA) assay on prospectively collected plasma samples (n = 555) from 69 patients with advanced melanoma was performed. Patients were divided into three cohorts: cohort A (N = 30), stage III patients receiving adjuvant ICI/observation; cohort B (N = 29), unresectable stage III/IV patients receiving ICI therapy; and cohort C (N = 10), stage III/IV patients on surveillance after planned completion of ICI therapy for metastatic disease. RESULTS: In cohort A, compared to molecular residual disease (MRD)-negative patients, MRD-positivity was associated with significantly shorter distant metastasis-free survival (DMFS; hazard ratio [HR], 10.77; p = .01). Increasing ctDNA levels from the post-surgical or pre-treatment time point to after 6 weeks of ICI were predictive of shorter DMFS in cohort A (HR, 34.54; p < .0001) and shorter progression-free survival (PFS) in cohort B (HR, 22; p = .006). In cohort C, all ctDNA-negative patients remained progression-free for a median follow-up of 14.67 months, whereas ctDNA-positive patients experienced disease progression. CONCLUSION: Personalized and tumor-informed longitudinal ctDNA monitoring is a valuable prognostic and predictive tool that may be used throughout the clinical course of patients with advanced melanoma.

Atypical Fibroxanthoma: Outcomes from a Large Single Institution Series.

BACKGROUND: Atypical fibroxanthomas (AFX) are rare malignant cutaneous neoplasms. Unfortunately, limited clinicopathologic and outcomes data on this cancer exists. OBJECTIVE: We report the clinical, pathologic, and treatment characteristics, as well as oncologic outcomes in this single-institution retrospective analysis. METHODS: This retrospective cohort study compiled clinical, pathologic, treatment, and outcome data for all patients with AFX on definitive excision diagnosed, evaluated, and treated primarily by surgical resection at a single institution between 2000-2020. Descriptive statistics evaluated clinical and pathologic characteristics. Kaplan-Meier method and Cox proportional-hazards models were used to evaluate overall survival and recurrence-free survival. RESULTS: 78 patients with AFX were identified. The majority were elderly, immunocompetent, Caucasian men. 85% of tumors were located on the head and neck. 63% of patients were correctly diagnosed only after complete resection of the index lesion. The median surgical margin was 1.0 cm. Overall, only 1.3% (1/78) of patients developed a local recurrence (RFS). No patients died of disease. CONCLUSION: This study suggests that resection margins of 1 cm achieve excellent local control with close to 99% RFS and 100% disease-specific survival.

Interobserver agreement in the histopathological classification of desmoplastic melanomas.

Desmoplastic melanoma is a subtype of melanoma characterised by amelanotic fusiform melanocytes dispersed in a collagenous stroma. Cell-poor and fibrous stroma-rich 'pure' variants have been distinguished from 'mixed' variants with areas of higher cell density and/or less desmoplastic stroma. This distinction is relevant because patients whose tumours display a pure phenotype have a lower risk for regional lymph node metastasis and distant recurrence. However, little is known about interobserver agreement among pathologists in the subclassification of desmoplastic melanoma. To address this issue, we conducted a study in which eleven dermatopathologists independently evaluated whole slide scanned images of excisions from 30 desmoplastic melanomas. The participating pathologists were asked to classify the tumours as pure or mixed. They were also asked to record the presence or absence of neurotropism and angiotropism. We found substantial interobserver agreement between the 11 dermatopathologists in the classification of tumours as pure versus mixed desmoplastic melanoma (kappa=0.64; p<0.0001). There was fair agreement between the 11 dermatopathologists in the evaluation of presence versus absence of neurotropism (kappa=0.26; p<0.0001), and slight agreement in the assessment of angiotropism (kappa=0.13; p<0.0001). The level of concordance in the subclassification of desmoplastic melanomas is encouraging for the acceptance of this prognostic parameter in the real-world practice of melanoma pathology.

Fucosylation of HLA-DRB1 regulates CD4+ T cell-mediated anti-melanoma immunity and enhances immunotherapy efficacy.

Immunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs); thus, effective strategies to safely increase itICs are needed. We report that dietary administration of L-fucose induces fucosylation and cell surface enrichment of the major histocompatibility complex (MHC)-II protein HLA-DRB1 in melanoma cells, triggering CD4+ T cell-mediated increases in itICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance and anti-programmed cell death protein 1 (PD1) responder status in patient melanoma specimens, suggesting the potential use of melanoma fucosylation as a strategy for stratifying patients for immunotherapies. Our findings demonstrate that fucosylation is a key mediator of anti-tumor immunity and, importantly, suggest that L-fucose is a powerful agent for safely increasing itICs and immunotherapy efficacy in melanoma.