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Museums that commemorate war have a uniquely influential role in determining how the nation approaches its past, and navigate highly politicized issues of loss and victimhood. Far less understood is how curatorial approaches to historical conflicts can influence museum practices regarding more recent wars. In this article, we explore how three museums of national history in Serbia narrate historical wars. Each museum is focused on articulating the story of the nation, albeit with markedly differing emphases in their collecting practices and curatorial strategies. Analysing objects and narrative texts, we suggest that Serbian historical museums engage visitors in ethical questions and topics that are often otherwise silenced. We draw attention to the resurgence of deep historical narratives, emphasizing Serbs’ connection to the environment, faith, and landscape, as a means to assert the continued relevance of historical wars to contemporary national identity. In doing so, museums seek to engage in the fraught politics of memory relating to the Yugoslav Wars.

Recent studies demonstrate a short 3–6-month atmospheric lifetime for mercury (Hg). This implies Hg emissions are predominantly deposited within the same hemisphere in which they are emitted, thus placing increasing importance on considering Hg sources, sinks and impacts from a hemispheric perspective. In the absence of comprehensive Hg data from the Southern Hemisphere (SH), estimates and inventories for the SH have been drawn from data collected in the NH, with the assumption that the NH data are broadly applicable. In this paper, we centre the uniqueness of the SH in the context of natural biogeochemical Hg cycling, with focus on the midlatitudes and tropics. Due to its uniqueness, Antarctica warrants an exclusive review of its contribution to the biogeochemical cycling of Hg and is therefore excluded from this review. We identify and describe five key natural differences between the hemispheres that affect the biogeochemical cycling of Hg: biome heterogeneity, vegetation type, ocean area, methylation hotspot zones and occurence of volcanic activities. We review the current state of knowledge of SH Hg cycling within the context of each difference, as well as the key gaps that impede our understanding of natural Hg cycling in the SH. The differences demonstrate the limitations in using NH data to infer Hg processes and emissions in the SH.

Understanding the evolutionary pathways to metastasis and resistance to immune-checkpoint inhibitors (ICI) in melanoma is critical for improving outcomes. Here, we present the most comprehensive intrapatient metastatic melanoma dataset assembled to date as part of the Posthumous Evaluation of Advanced Cancer Environment (PEACE) research autopsy program, including 222 exome sequencing, 493 panel-sequenced, 161 RNA sequencing, and 22 single-cell whole-genome sequencing samples from 14 ICI-treated patients. We observed frequent whole-genome doubling and widespread loss of heterozygosity, often involving antigen-presentation machinery. We found KIT extrachromosomal DNA may have contributed to the lack of response to KIT inhibitors of a KIT-driven melanoma. At the lesion-level, MYC amplifications were enriched in ICI nonresponders. Single-cell sequencing revealed polyclonal seeding of metastases originating from clones with different ploidy in one patient. Finally, we observed that brain metastases that diverged early in molecular evolution emerge late in disease. Overall, our study illustrates the diverse evolutionary landscape of advanced melanoma.Significance:Despite treatment advances, melanoma remains a deadly disease at stage IV. Through research autopsy and dense sampling of metastases combined with extensive multiomic profiling, our study elucidates the many mechanisms that melanomas use to evade treatment and the immune system, whether through mutations, widespread copy-number alterations, or extrachromosomal DNA.

Supplementary figure 1: Cohort overview. Number of samples sequenced with whole exome, panel or whole RNA sequencing. Supplementary figure 2: Phylogeny and WGD events in CRUKP1047. Supplementary figure 3: Ploidy and SCNA burden. Supplementary figure 4: Overview of each case. Supplementary figure 5: MEDICC2 copy number sample trees. Supplementary figure 6: MEDICC tree of all exome samples demonstrating that samples cluster together by patient, and not by melanoma subtype. Supplementary figure 7: SCNA frequency of cutaneous (a), acral (b) and melanoma of unknown primary (MUP, c). Supplementary figure 8: Correlation between liver copy number distance to other sites and time of emergence after stage IV diagnosis. Supplementary figure 9: Examination of tumour heterogeneity of alterations to antigen-presentation machinery genes, with site and patient annotation. Supplementary figure 10: Boxplots indicating the proportion of losses in the cohort for each segment. Supplementary figure 11: Balance of expression between nonsynonymous mutations that were not predicted to be neoantigens and clonal predicted neoantigens. Supplementary figure 12: Barplot of TIL infiltration score frequencies, determined by pathologist assessment of histology, across all samples. Supplementary figure 13: Number of samples per patient that are classified as either none-low in terms of TILs or moderate-heavy. Supplementary figure 14: Histogram of purity for samples with RNA-seq data. Supplementary figure 15: TME deconvolution. Supplementary figure 16: The effect of metastatic site on transcriptional profiles. Supplementary figure 17: Association of PHF3 copy number with expression. Supplementary figure 18: Overview of gene fusions identified in RNA-seq data. Supplementary figure 19: Comparison of ploidy estimates from panel sequencing data, exome data and FISH. Supplementary figure 20: Comparison of ploidy estimates in panel, exome, FISH and single cell data. Supplementary figure 21: FACs sort plot for CRUKP2567 diaphragmatic metastasis. Supplementary figure 22: Ploidy and wGII values from single cell sequencing of FACS-sorted tumour cells. Supplementary figure 23: Copy number profiles on chromosome 5 for bulk samples from primary and DI_2_R2, a diaphragmatic metastasis. Supplementary figure 24: Histogram of purity of samples for which RNA-seq was performed faceted by patient. Supplementary figure 25: Histogram of purity of samples for which RNA-seq was performed faceted by tissue site.

S. Table 1: List of PEACE Consortium members. S. Table 2: Sample database used for the study for Panel, Exome and RNASeq samples. S. Table 3: Overview of lines of treatment given to each patient. S. Table 4: Lesions and patients included in the lesion-level response to ICI analysis. S. Table 5: Hallmark genesets significantly upregulated in normal tissue vs tumor tissue. Table shows p-values for tissue type, purity; T value for tissue type, purity; q-value for tissue type, purity (FDR corrected). S. Table 6: Hallmark genesets significantly upregulated in tumor tissue vs normal tissue. Table shows p-values for tissue type, purity; T value for tissue type, purity; q-value for tissue type, purity (FDR corrected). S. Table 7: Genes included in the target panel. S. Table 8: Tree topology comparisons between manually constructed trees and pairtree-constructed trees.

There have been extensive studies of the struggles against Latin American military dictatorships of the 1960s and 1980s, especially regarding the activism of mothers of political activists who were disappeared. However there has been far less research about women’s continued struggle for memory, truth, and justice in contemporary Latin America. There has been even less consideration of how small-scale urban protesters use memory within urban cultural geographies of activism. This article explores the production of political memory by mothers of victims of state violence in Rio de Janeiro. The mother’s struggle encompasses heritage practices in favelas, as well as in the central business district, but deliberately recall and amplify the claims for justice from the 1960s and 1980s. This recalls not only the heritage connected with the dictatorship, but situates their practices within activists’ lived experiences of the colonial state and its attempts to render their murdered children criminals. Resumen: “Luchamos por la memoria de nuestros hijos”: Memoria política, patrimonio de favela y madres de víctimas de violencia estatalExisten amplios estudios sobre las luchas contra las dictaduras militares latinoamericanas de los años sesenta y ochenta, sobretodo sobre el activismo de las madres de los activistas políticos desaparecidos. Sin embargo, apenas se ha investigado la continua lucha de las mujeres por la memoria, la verdad y la justicia en la América Latina contemporánea; y aún menos cómo los manifestantes urbanos a pequeña escala utilizan la memoria dentro de las geografías culturales urbanas del activismo. Este artículo explora la producción de memoria política por parte de las madres de las víctimas de la violencia estatal en Río de Janeiro. Su lucha abarca prácticas patrimoniales en las favelas y en el distrito comercial central, pero recuerda y amplifica deliberadamente las reivindicaciones de justicia de los años sesenta y ochenta. No solo recuerda la herencia relacionada con la dictadura, sino que sitúa sus prácticas dentro de las experiencias vividas por los activistas del estado colonial y sus intentos de convertir a sus hijos asesinados en criminales.

After the end of Latin American dictatorships, scholars closely analyzed the relationship between violence, memory and democracy. But these societies have continued to grapple not only with the legacy of authoritarian governments but with centuries of colonial power, with the result that many of the assumptions of earlier scholars are now being revisited. Intersectional questions of race, indigeneity and gender continue to refashion our understanding of memory and injustice. These questions frame this introductory article, in which we argue that Latin American contemporary social mobilisation that has denounced recent and long-term violence is constituted through intervention and creation of heritage from below. We propose that the interdisciplinary field of Critical Heritage Studies, that has burgeoned recently in the region, offers a means to understand how space, scale, and society interact to create meanings and work through violent pasts. The works of this Special Collection extend traditional conceptions of urban heritage as the mere conservation of cities’ landscape, towards the study of the relation between cultural geographies and the production of social mobilizations in Latin America. These geographies enable unique formulations of protest for activists, creating new capacities to contest recent and long-term human rights abuse. Resumen: Herencia desde abajo en Latinoamérica: Protestas urbanas y la lucha por los Derechos HumanosTras el fin de las dictaduras latinoamericanas, las/os académicos de la región analizaron de cerca la relación entre violencia, memoria y democracia. Pero estas sociedades han seguido lidiando con el legado de los gobiernos autorita-rios y con siglos de abuso colonial, por lo que muchos de los supuestos de estos primeros estudios ahora están siendo examinados. Preguntas sobre la interseccionalidad racial, indígena y de género continúan reformulando nuestra comprensión sobre la relación entre la memoria y la injusticia. Estas preguntas guían este artículo introductorio, en el que sostenemos que la movilización social contemporánea en Latinoamérica que ha denunciado las violencias recientes y de larga data se constituyen a través de la intervención y la creación de patrimonio desde abajo. Proponemos que el campo interdisciplinario de Estudios Críticos del Patrimonio, que ha florecido recientemente en la región, ofrece un medio para comprender cómo el espacio, sus diferentes escalas y la sociedad interactúan para crear significados y elaborar sus pasados de violencia y opresión. Los trabajos de este número especial amplían las concepciones tradicionales del patrimonio urbano como la mera conservación del paisaje de las ciudades, hacia el estudio de la relación entre geografías culturales y la producción y performance de movilizaciones sociales en la región. Estas geografías constituyen de forma única las protestas y sus significados, creando nuevas capacidades para luchar en contra de las violencias recientes y coloniales.

Purpose: The adenoids, or pharyngeal tonsils, consist of a pad of lymphoid tissue, located on the posterior pharyngeal wall of the nasopharynx. During childhood, the adenoid pad serves as a contact site for the soft palate to assist with velopharyngeal closure during oral speech. During adenoidal involution, most children are able to maintain appropriate velopharyngeal closure necessary for normal speech resonance. The purpose of this study is to determine age-related trends of normal adenoid growth and involution from infancy through adulthood. Method/Description: Lateral view magnetic resonance imaging was used to analyze velopharyngeal variables among 270 participants, between 3 months and 34 years of age. The velopharyngeal measures of interest included velar length, effective velar length, pharyngeal depth, adenoid height, adenoid thickness, adenoid depth, and adenoid area. Participants were divided into four age groups for statistical comparison. Results: There was a statistically significant difference ( p < .05) in all linear and area measurements between the four age groups. Adenoid depth reached peak growth at age 4 years, whereas adenoid height and adenoid thickness peaked at 8 years of age. Qualitatively, adenoid growth progresses in an anterior and inferior direction whereas involution occurs in a posterior and superior direction. Conclusions: This study contributes to the knowledge of time specific changes across an age span for adenoid growth and involution and presents a visualization of the shape and growth trends of adenoids. A new sequence of involution is reported beginning first with adenoid depth, followed by adenoid height at a slightly faster rate than adenoid thickness.

Mason explores Saudi-Iranian rivalry in the Middle East with particular reference to the growth in political contentions post-1979. He covers work by Ghattas who provides a more social perspective on the fallout from increased Saudi-Iranian rivalry from 1979, including sectarian violence from Egypt through to Pakistan, and a more policy-orientated appraisal and outline for conflict resolution between the parties provided by Fraihat. Taken together, they afford a comprehensive overview of the causes and effects of this “conflict.” For a political science scholar, it is Fraihat who tackles substantive conflict resolution issues of enduring concern: rebalancing the regional order, reforming conflict strategies, mediation, Track II diplomacy, and bottom up peace-building, which may hold the keys to shaping the next four decades in more peaceful ways than the previous four. Given the limited avenues of exploration in these areas, a partial GCC state backlash against the Joint Comprehensive Plan of Action (JCPOA) during the Obama administration, and the political consolidation underway in both states, one might despair of a breakthrough. The Biden administration represents an opportunity to at least contemplate de-escalation measures resulting from talks such as those underway in Iraq in 2021. Meanwhile, the policies of small states such as Oman and Qatar provide insights on pragmatic foreign policy behavior, some of which could be replicated by the key protagonists.

Coral bleaching can have widespread impacts on reefs leaving many areas in need of coral recovery. While the long-term mitigation of bleaching requires transitioning to a low carbon economy, local management has focused on approaches that seek refugia from or tolerance to bleaching stressors, reduce additional stressors, or facilitate coral recovery. Here, we describe a tactical response to coral bleaching events that seeks to identify the most important reefs for driving imminent recovery. A bleaching recovery algorithm is described that identifies those reefs that provide the most important sources of coral larvae that supply many reefs in the early stages of post-bleaching recovery (i.e., reefs in need of coral larval supply). We describe the algorithm with a simple toy example and then apply it to the Great Barrier Reef, which has experienced three mass bleaching events in the last 5 yr. Once such reefs have been identified it makes practical sense to undertake a vulnerability assessment and if necessary reduce manageable stressors, such as outbreaks of crown-of-thorns starfish or anchor damage, so that critical sources of coral recovery are not depleted further. In short, algorithms like this can help managers target finite management resources, including restoration, to where they might be most effective in facilitating natural processes of recovery.

In this article, we analyse Indian museum practices that pertain to the representation of the nation’s liberation and independence from colonial occupation. We draw specifically on a comparative analysis of museums in the former Portuguese and French territories of India. These territories remained colonies for a number of years after the British were forced from India, raising questions of how contemporary museums represent these alternative narratives of independence. Such sites have previously been considered at the periphery of narratives of Indian decolonisation, but we argue that the territories reveal key aspects of current museological practice in India. In examining how museums in Velha Goa and Chandannagar represent colonial narratives, we demonstrate that the museums present a timeless and enduring Indian culture that has universal values, contrasted with the temporally limited European nature of imperialism. We subsequently argue that museum practices, which might appear to diverge from the central narrative of Indian independence, have instead been co-opted to support historical narratives of an essentialised Indian state and singular emergence as an independent nation.

Introduction The Cancer Urgent Assessment Clinic (CUAC) was an emergency department (ED) avoidance/unscheduled model of care implemented in response to the COVID-19 pandemic. The aim was to reduce the risk of COVID-19 exposure and infection by providing an alternative to ED for cancer patients while undergoing anticancer treatments. Methods The clinic incorporated a telephone triage process and face-to-face appointments 8am to 8pm, 7 days per week. CUAC operated between 23 March '20 and 31 July '20, led by a nurse practitioner candidate, oncology registrars, cancer nurse specialists, and overseen by oncology consultants. Evaluation followed a mixed-methods approach through (1) analysis of CUAC patient data, (2) comparison of ED cancer patient presentation data from a previous period (23 March 2019–31 July 2019), and (3) a patient survey. Results In total, 400 patients were telephone triaged via CUAC, with 166 recorded as having avoided ED. There was a reduction in the number of cancer patient admissions to the ED short stay unit during the clinic period compared with the same time-period in 2019: 130 vs. 234, associated with 615 fewer hours. Patient satisfaction was positive particularly regarding ease of access, time to treatment, confidence in assessment and treatment of cancer-related concerns, and likelihood of presenting to hospital when unwell during the pandemic. Discussion While initially being implemented to reduce the risk of COVID-19 exposure, this evaluation demonstrated the CUAC model was an efficient and potentially cost-saving model of care for the management of cancer patients with mild to moderate severity of disease and treatment-related concerns.

Gene copy number variation across individuals has been shown to track population structure and be a source of adaptive genetic variation with significant fitness impacts. In this study, we report opposite results for both predictions based on the analysis of gene copy number variants (CNVs) of Suillus brevipes, a mycorrhizal fungus adapted to coastal and montane habitats in California. In order to assess whether gene copy number variation mirrored population structure and selection in this species, we investigated two previously studied locally adapted populations showing a highly differentiated genomic region encompassing a gene predicted to confer salt tolerance. In addition, we examined whether copy number in the genes related to salt homeostasis was differentiated between the two populations. Although we found many instances of CNV regions across the genomes of S. brevipes individuals, we also found CNVs did not recover population structure and known salt-tolerance-related genes were not under selection across the coastal population. Our results contrast with predictions of CNVs matching single-nucleotide polymorphism divergence and showed CNVs of genes for salt homeostasis are not under selection in S. brevipes.

Horatio Nelson is one of the greatest English heroes. His key exploits at the battles of the Nile and Trafalgar, which led to Britain’s maritime supremacy, are well known and celebrated in the 5.5m statue at the summit of Nelson’s column in Trafalgar Square, London. The statue also showcases his most famous injuries, the injury to his right eye and arm amputation. However, as well as these he had a number of other battle injuries and afflictions including recurrent malaria, yellow fever, scurvy, tuberculosis and dysentery, which, although he bore with stoicism, may have affected his professional performance at different times in his career. The exact cause of his death was probably a combination of blood loss, lung injury and spinal shock.

Photoinduced isomerization reactions lie at the heart of many chemical processes in nature. The mechanisms of such reactions are determined by a delicate interplay of coupled electronic and nuclear dynamics occurring on the femtosecond scale, followed by the slower redistribution of energy into different vibrational degrees of freedom. Here we apply time-resolved photoelectron spectroscopy with a seeded extreme ultraviolet free-electron laser to trace the ultrafast ring opening of gas-phase thiophenone molecules following ultraviolet photoexcitation. When combined with ab initio electronic structure and molecular dynamics calculations of the excited- and ground-state molecules, the results provide insights into both the electronic and nuclear dynamics of this fundamental class of reactions. The initial ring opening and non-adiabatic coupling to the electronic ground state are shown to be driven by ballistic S–C bond extension and to be complete within 350 fs. Theory and experiment also enable visualization of the rich ground-state dynamics that involve the formation of, and interconversion between, ring-opened isomers and the cyclic structure, as well as fragmentation over much longer timescales.

The article draws on labour and migration histories of the early twentieth century to demonstrate how migrants’ land use was modified in the process of moving from rural Catalonia to northern Queen...

The residues from the internal surface of four archaeological ceramic sherds, excavated from the Armenian Gardens, Jerusalem were analysed to characterise the contents of the original vessel. The sherds derive from four small, thick-walled, sphero-conical vessels recovered from a destruction layer, dating between the 11th and 12th century, Jerusalem. The residue has been analysed using light microscopy, biochemical characterisation, gas chromatography mass spectroscopy, inductively coupled plasma atomic emission spectroscopy and cold vapour atomic fluorescence spectrometry. This analysis established the presence of various compounds including fatty acids and notable levels of mercury, sulphur, aluminium, potassium, magnesium, nitrates and phosphorous. The contents and probable functions of the four vessels were characterised from the residues on these sherds as different from each other, reflecting their different decoration, manufacture and ceramic typologies. One of these vessels contains residue that indicate the vessel held oils. The residue of the second vessel is consistent with either scented materials or medicinal contents, while a third probably contained medicinal material. The unique fourth sherd is from a stoneware sphero-conical vessel with very thick walls, no decoration and the residue supports the possibility it was used for the storage of chemicals or may have held the chemical ingredients for an explosive device, consistent with a medieval grenade. This residue analysis of Mamluk sphero-conical vessels provides insight into luxury items, medicines, technology and trade in medieval Jerusalem.

Cumulative impacts assessments on marine ecosystems have been hindered by the difficulty of collecting environmental data and identifying drivers of community dynamics beyond local scales. On coral reefs, an additional challenge is to disentangle the relative influence of multiple drivers that operate at different stages of coral ontogeny. We integrated coral life history, population dynamics and spatially-explicit environmental drivers to assess the relative and cumulative impacts of multiple stressors across 2,300 km of the world’s largest coral reef ecosystem, Australia’s Great Barrier Reef (GBR). Using literature data, we characterized relationships between coral life history processes (reproduction, larval dispersal, recruitment, growth and mortality) and environmental variables. We then simulated coral demographics and stressor impacts at the organism (coral colony) level on >3,800 individual reefs linked by larval connectivity, and exposed to temporally- and spatially-realistic regimes of acute (crown-of-thorns starfish outbreaks, cyclones and mass coral bleaching) and chronic (water quality) stressors. Model simulations produced a credible reconstruction of recent (2008–2020) coral trajectories consistent with monitoring observations, while estimating the impacts of each stressor at reef and regional scales. Overall, corals declined by one third across the GBR, from an average ∼29% to ∼19% hard coral cover. By 2020, less than 20% of the GBR had coral cover higher than 30%. Global annual rates of coral mortality were driven by bleaching (48%) ahead of cyclones (41%) and starfish predation (11%). Beyond the reconstructed status and trends, the model enabled the emergence of complex interactions that compound the effects of multiple stressors while promoting a mechanistic understanding of coral cover dynamics. Drivers of coral cover growth were identified; notably, water quality (suspended sediments) was estimated to delay recovery for at least 25% of inshore reefs. Standardized rates of coral loss and recovery allowed the integration of all cumulative impacts to determine the equilibrium cover for each reef. This metric, combined with maps of impacts, recovery potential, water quality thresholds and reef state metrics, facilitates strategic spatial planning and resilience-based management across the GBR.

Background: Studies suggest that combining radiotherapy (RT) with programmed cell death protein 1 (PD-1) blockade may elicit a synergistic antitumor response. We aimed to assess whether prior or concurrent RT was associated with improved disease control in patients with metastatic non-small cell lung cancer (NSCLC) treated with nivolumab. Methods: We conducted a retrospective study of patients receiving nivolumab as second or subsequent line therapy for metastatic NSCLC. Patients were categorized into those who received any RT for NSCLC prior to or during nivolumab therapy, and those with no history of RT for NSCLC. Results: A total of 85 patients received nivolumab between July 2015 and December 2016 and were followed up for a median of 15 months. Sixty-five patients (76.4%) received RT prior to or during nivolumab and 20 patients (23.6%) received nivolumab alone. Baseline characteristics of age, performance status, histology, smoking status and previous therapy were similar between the two groups. Prior or concurrent RT was associated with a superior PFS, median 2.8 months with RT versus 1.3 months without RT (Hazard Ratio (HR) = 0.494; 95% Confidence Interval (CI), 0.279-0.873; P = 0.02). The median OS of the group receiving RT was 6.4 months versus 4.2 months for the no RT group (P = 0.20). RT was not associated with an increase in toxicity. Conclusion: RT prior to or concurrent with nivolumab for metastatic NSCLC was associated with a modest improvement in PFS over nivolumab alone with no evidence of increase in adverse effects. RT may potentiate the effect of anti-PD-1 immunotherapy in NSCLC.

On May 5th, 1862, heavily outnumbered Mexican troops succeeded in defeating the invading French army at the Battle of Puebla. The battle did little to change the war’s outcome, but became a powerful symbol of Mexican national unity that helped to make sense of the violence of the previous decades. Celebrations to commemorate the Cinco de Mayo began almost as soon as the battle had ended, and have since evolved in Puebla to become one of the city’s pre-eminent expressions of civic identity. This article explores the evolution of the battle’s commemorations over a five-year period, during which the city invested in multiple new museums and tourist infrastructure connected to the iconic events. The article focuses on two key heritage precincts, containing six museums that were central to attempts to transform the historic city centre. The article explores how attempts to co-opt historic suffering was used to frame a narrative of civic democracy and inclusion. In so doing, it signals the role of state-level governments in curating a nationally significant memory. It also suggests a need for caution as government co-opts multiple stories into a means to augment its own authority.

SummaryAntigen recognition and T-cell mediated cytotoxicity in clear-cell renal cell carcinoma (ccRCC) remains incompletely understood. To address this knowledge gap, we analysed 115 multiregion tumour samples collected from 15 treatment-naïve patients pre- and post-nivolumab therapy, and at autopsy in three patients. We performed whole-exome sequencing, RNAseq, TCRseq, multiplex immunofluorescence and flow cytometry analyses and correlated with clinical response. We observed pre-treatment intratumoural TCR clonal expansions suggesting pre-existing immunity. Nivolumab maintained pre-treatment expanded, clustered TCR clones in responders, suggesting ongoing antigen-driven stimulation of T-cells. T-cells in responders were enriched for expanded TCF7+CD8+T-cells and upregulated GZMK/B upon nivolumab-binding. By contrast, nivolumab promoted accumulation of new TCR clones in non-responders, replacing pre-treatment expanded clonotypes. In this dataset, mutational features did not correlate with response to nivolumab and human endogenous retrovirus expression correlated indirectly. Our data suggests that nivolumab potentiates clinical responses in ccRCC by binding pre-existing expanded CD8+T-cells to enhance cytotoxicity.