tbuckley/cabot-search huggingface dataset:
Autoinflammation in patients with leukocytic CBL loss of heterozygosity is caused by constitutive ERK-mediated monocyte activation
Authors: Jonathan Bohlen, Ivan Bagarić, Taja Vatovec, Masato Ogishi, Syed F Ahmed, Axel Cederholm, Lori Buetow, Steicy Sobrino, Corentin Le Floc'h, Carlos A Arango-Franco, Luis Seabra, Marine Michelet, Federica Barzaghi, Davide Leardini, Francesco Saettini, Francesca Vendemini, Francesco Baccelli, Albert Catala, Eleonora Gambineri, Marinella Veltroni, Yurena Aguilar de la Red, Gillian I Rice, Filippo Consonni, Laureline Berteloot, Laetitia Largeaud, Francesca Conti, Cécile Roullion, Cécile Masson, Boris Bessot, Yoann Seeleuthner, Tom Le Voyer, Darawan Rinchai, Jérémie Rosain, Anna-Lena Neehus, Lucia Erazo-Borrás, Hailun Li, Zarah Janda, En-Jui Cho, Edoardo Muratore, Camille Soudée, Candice Lainé, Eric Delabesse, Claire Goulvestre, Cindy S Ma, Anne Puel, Stuart G Tangye, Isabelle André, Christine Bole-Feysot, Laurent Abel, Miriam Erlacher, Shen-Ying Zhang, Vivien Béziat, Chantal Lagresle-Peyrou, Emmanuelle Six, Marlène Pasquet, Laia Alsina, Alessandro Aiuti, Peng Zhang, Yanick J Crow, Nils Landegren, Riccardo Masetti, Danny T Huang, Jean-Laurent Casanova, Jacinta Bustamante
Journal: Journal of Clinical Investigation (2024)

Patients heterozygous for germline CBL loss-of-function (LOF) variants can develop myeloid malignancy, autoinflammation, or both, if some or all of their leukocytes become homozygous for these variants through somatic loss of heterozygosity (LOH) via uniparental isodisomy. We observed an upregulation of the inflammatory gene expression signature in whole blood from these patients, mimicking monogenic inborn errors underlying autoinflammation. Remarkably, these patients had constitutively activated monocytes that secreted 10 to 100 times more inflammatory cytokines than those of healthy individuals and CBL LOF heterozygotes without LOH. CBL-LOH hematopoietic stem and progenitor cells (HSPCs) outgrew the other cells, accounting for the persistence of peripheral monocytes homozygous for the CBL LOF variant. ERK pathway activation was required for the excessive production of cytokines by both resting and stimulated CBL-LOF monocytes, as shown in monocytic cell lines. Finally, we found that about 1 in 10,000 individuals in the UK Biobank were heterozygous for CBL LOF variants and that these carriers were at high risk of hematological and inflammatory conditions.
Sustained but Decoyed Activation of the JAK1-STAT Pathway by Aberrant Protein Aggregation Exacerbates Proteotoxicity
Authors: Mingqi Cai, Bo Pan, Peng Xiao, Mark Bouska, Megan T. Lewno, Yu Xing, Erliang Zeng, Huiyun Liang, Faqian Li, Xiang Gao, Xuejun Wang
Journal: Circulation (2024)
Timing of antiretroviral therapy initiation affects intact HIV reservoirs following analytical treatment interruption
Authors: Maegan R Manning, Jana Blazkova, Jesse S Justement, Victoria Shi, Brooke D Kennedy, M Ali Rai, Catherine A Seamon, Kathleen Gittens, Michael C Sneller, Susan Moir, Tae-Wook Chun
Journal: Journal of Clinical Investigation (2024)
HOPE springs eternal: lack of HIV superinfection in HIV Organ Policy Equity Act kidney transplants
Authors: Christine M Durand, Andrew D Redd
Journal: Journal of Clinical Investigation (2024)

Kidney transplantation from donors with HIV to recipients with HIV (HIV D+/R+) is an emerging practice that has shown substantial clinical benefit. Sustained HIV superinfection, whereby a transplant recipient acquires a new strain of HIV from their organ donor, is a theoretical risk, which might increase chances of viral failure. In this issue of the JCI, Travieso, Stadtler, and colleagues present phylogenetic analysis of HIV from kidney tissue, urine, plasma, and cells from 12 HIV D+/R+ kidney transplants out to five years of follow-up. Early after transplant, donor HIV was transiently detected in five of 12 recipients, primarily from donors with untreated HIV and high-level viremia, consistent with a viral inoculum. Long-term, donor HIV was not detected in any recipients, demonstrating no sustained HIV superinfection. These reassuring data support earlier findings from South Africa and the United States and further confirm the safety of HIV D+/R+ transplantation.
Deficiency of parkin causes neurodegeneration and accumulation of pathological α-synuclein in monkey models
Authors: Rui Han, Qi Wang, Xin Xiong, Xiusheng Chen, Zhuchi Tu, Bang Li, Fei Zhang, Chunyu Chen, Mingtian Pan, Ting Xu, Laiqiang Chen, Zhifu Wang, Yanting Liu, Dajian He, Xiangyu Guo, Feng He, Peng Wu, Peng Yin, Yunbo Liu, Xiaoxin Yan, Shihua Li, Xiao-Jiang Li, Weili Yang
Journal: Journal of Clinical Investigation (2024)

Parkinson's disease (PD) is characterized by age-dependent neurodegeneration and the accumulation of toxic phosphorylated α-synuclein (pS129-α-syn). The mechanisms underlying these crucial pathological changes remain unclear. Mutations in parkin RBR E3 ubiquitin protein ligase (PARK2), the gene encoding parkin that is phosphorylated by PTEN-induced putative kinase 1 (PINK1) to participate in mitophagy, cause early onset PD. However, current parkin-KO mouse and pig models do not exhibit neurodegeneration. In the current study, we utilized CRISPR/Cas9 technology to establish parkin-deficient monkey models at different ages. We found that parkin deficiency leads to substantia nigra neurodegeneration in adult monkey brains and that parkin phosphorylation decreases with aging, primarily due to increased insolubility of parkin. Phosphorylated parkin is important for neuroprotection and the reduction of pS129-α-syn. Consistently, overexpression of WT parkin, but not a mutant form that cannot be phosphorylated by PINK1, reduced the accumulation of pS129-α-syn. These findings identify parkin phosphorylation as a key factor in PD pathogenesis and suggest it as a promising target for therapeutic interventions.
Muscle Mass and Glucagon-Like Peptide-1 Receptor Agonists: Adaptive or Maladaptive Response to Weight Loss?
Authors: Jennifer Linge, Andreas L. Birkenfeld, Ian J. Neeland
Journal: Circulation (2024)

Recent studies have shown that pharmacologic weight loss with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and combination therapies is approaching magnitudes achieved with surgery. However, as more weight loss is achieved, there is concern for potential adverse effects on muscle quantity, composition, and function. This primer aims to address whether muscle-related changes associated with weight loss treatments such as GLP-1 RAs may be maladaptive (ie, adversely affecting muscle health or function), adaptive (ie, a physiologic response to weight loss maintaining or minimally affecting muscle health or function), or perhaps an enhanced response to weight loss (ie, improved muscle health or function after treatment). Based on contemporary evidence with the addition of studies using magnetic resonance imaging, skeletal muscle changes with GLP-1 RA treatments appear to be adaptive: changes in muscle volume z-score indicate a change in muscle volume that is commensurate with what is expected given aging, disease status, and weight loss achieved, and the improvement in insulin sensitivity and muscle fat infiltration likely contributes to an adaptive process with improved muscle quality, lowering the probability for loss in strength and function. Nevertheless, factors such as older age and prefrailty may influence the selection of appropriate candidates for these therapies because of risk for sarcopenia. Several pharmacologic treatments to maintain or improve muscle mass designed in combination with GLP-1–based therapies are under development. For future development of GLP-1–based therapies (and other therapies) designed for weight loss, as well as for patient-centered treatment optimization, the introduction of more objective and comprehensive ways of assessing muscle health (including accurate and meaningful assessments of muscle quantity, composition, function, mobility, and strength) is important for the substantial numbers of patients who will likely be taking these medications well into the future.
Optical Spectroscopic Detection and Typing of Cardiac Amyloidosis
Authors: Sudipta S. Mukherjee, Joseph J. Maleszewski, Daniel Luthringer, Matthew P. Confer, Anirudh Mittal, Surendra Dasari, Ellen D. McPhail, Suraj Kapa, Thenkurussi Kesavadas, Andre Kajdacsy-Balla, Evan Kransdorf, Jai Raman, Rohit Bhargava
Journal: Circulation (2024)
Functional variation in human CAZyme genes in relation to the efficacy of a carbohydrate-restricted diet in IBS patients
Authors: Andreea Zamfir-Taranu, Britt-Sabina Löscher, Florencia Carbone, Abdullah Hoter, Cristina Esteban Blanco, Isotta Bozzarelli, Leire Torices, Karen Routhiaux, Karen Van den Houte, Ferdinando Bonfiglio, Gabriele Mayr, Maura Corsetti, Hassan Y Naim, Andre Franke, Jan Tack, Mauro D'Amato
Journal: Clinical Gastroenterology and Hepatology (2024)

Limiting the dietary intake of certain carbohydrates has therapeutic effects in some but not all irritable bowel syndrome (IBS) patients. We investigated genetic variation in human Carbohydrate-Active enZYmes (hCAZymes) genes in relationship to the response to a FODMAP-lowering diet in the DOMINO study.
Opportunities for Innovation in Smoking Cessation Therapies: A Perspective From the National Institutes of Health and U.S. Food and Drug Administration
Authors: Haider J. Warraich, Brian A. King, Wilson M. Compton, Evan S. Herrmann, Mary Thanh Hai, Robert M. Califf, Monica M. Bertagnolli
Journal: Annals of Internal Medicine (2024)
Regulation of CD8+ T cells by lipid metabolism in cancer progression
Authors: Yong Tang, Ziqing Chen, Qianying Zuo, Yibin Kang
Journal: Cellular and Molecular Immunology (2024)

Dysregulation of lipid metabolism is a key characteristic of the tumor microenvironment, where tumor cells utilize lipids for proliferation, survival, metastasis, and evasion of immune surveillance. Lipid metabolism has become a critical regulator of CD8+ T-cell-mediated antitumor immunity, with excess lipids in the tumor microenvironment impeding CD8+ T-cell activities. Considering the limited efficacy of immunotherapy in many solid tumors, targeting lipid metabolism to enhance CD8+ T-cell effector functions could significantly improve immunotherapy outcomes. In this review, we examine recent findings on how lipid metabolic processes, including lipid uptake, synthesis, and oxidation, regulate CD8+ T cells within tumors. We also assessed the impact of different lipids on CD8+ T-cell-mediated antitumor immunity, with a particular focus on how lipid metabolism affects mitochondrial function in tumor-infiltrating CD8+ T cells. Furthermore, as cancer is a systemic disease, we examined systemic factors linking lipid metabolism to CD8+ T-cell effector function. Finally, we summarize current therapeutic approaches that target lipid metabolism to increase antitumor immunity and enhance immunotherapy. Understanding the molecular and functional interplay between lipid metabolism and CD8+ T cells offers promising therapeutic opportunities for cancer treatment.
Macrophage diversity in cancer dissemination and metastasis
Authors: Alberto Mantovani, Federica Marchesi, Diletta Di Mitri, Cecilia Garlanda
Journal: Cellular and Molecular Immunology (2024)

Invasion and metastasis are hallmarks of cancer. In addition to the well-recognized hematogenous and lymphatic pathways of metastasis, cancer cell dissemination can occur via the transcoelomic and perineural routes, which are typical of ovarian and pancreatic cancer, respectively. Macrophages are a universal major component of the tumor microenvironment and, in established tumors, promote growth and dissemination to secondary sites. Here, we review the role of tumor-associated macrophages (TAMs) in cancer cell dissemination and metastasis, emphasizing the diversity of myeloid cells in different tissue contexts (lungs, liver, brain, bone, peritoneal cavity, nerves). The generally used models of lung metastasis fail to capture the diversity of pathways and tissue microenvironments. A better understanding of TAM diversity in different tissue contexts may pave the way for tailored diagnostic and therapeutic approaches.
Cardiovascular Disease Mortality Among Native Hawaiian and Pacific Islander Adults Aged 35 Years or Older, 2018 to 2022
Authors: Rebecca C. Woodruff, Joseph Keawe'aimoku Kaholokula, Lorinda Riley, Xin Tong, LaTonia C. Richardson, Kotryna Diktonaite, Fleetwood Loustalot, Adam S. Vaughan, Omoye E. Imoisili, Donald K. Hayes
Journal: Annals of Internal Medicine (2024)

Native Hawaiian and Pacific Islander (NHPI) adults have historically been grouped with Asian adults in U.S. mortality surveillance. Starting in 2018, the 1997 race and ethnicity standards from the U.S. Office of Management and Budget were adopted by all states on death certificates, enabling national-level estimates of cardiovascular disease (CVD) mortality for NHPI adults independent of Asian adults.
177Lu-PSMA-617 Radioligand Therapy in Patient With Prostate Cancer Sciatic Nerve Metastasis
Authors: David Tonnelet, Agathe Edet-Sanson, Laetitia Augusto, Marine Cabourg, Sébastien Thureau
Journal: Clinical Nuclear Medicine (2024)

Abstract Patients with metastatic castration-resistant prostate cancer usually have lymph nodes and bone metastasis. We present a rare case of a 51-year-old patient with metastatic castration-resistant prostate cancer who complained of left truncated sciatica and diffuse bone pain and who was referred for 177 Lu-prostate-specific membrane antigen (PSMA) screening. Pretreatment 68 Ga-PSMA showed left sciatic nerve and multiple bone uptake. Patient underwent stereotactic radiotherapy on the sciatic nerve metastasis (30 Gy in 6 fractions of 5 Gy) before 7.4 GBq of 177 Lu-PSMA infusions. Left truncated sciatica disappeared after stereotactic radiotherapy. No additional toxicity was added to the sciatic nerve from 177 Lu-PSMA after stereotactic radiotherapy.
Interchangeability of immune checkpoint inhibitors: an urgent need for action
Authors: Michiel Zietse, Roelof W F van Leeuwen, Sahar Barjesteh van Waalwijk van Doorn-Khosrovani, Jolanda E de Boer, Rudy Dupree, Ron H J Mathijssen, Lonneke Timmers
Journal: The Lancet Oncology (2024)
Perioperative chemotherapy and nivolumab in non-small-cell lung cancer (NADIM): 5-year clinical outcomes from a multicentre, single-arm, phase 2 trial
Authors: Mariano Provencio, Ernest Nadal, Amelia Insa, Rosario García Campelo, Joaquín Casal, Manuel Dómine, Bartomeu Massuti, Margarita Majem, Delvys Rodríguez-Abreu, Alex Martínez-Martí, Javier de Castro, David Gómez de Antonio, Iván Macia, Santiago Figueroa, Luís Fernández Vago, Virginia Calvo, Ramón Palmero, Belén Sierra-Rodero, Cristina Martínez-Toledo, Marta Molina-Alejandre, Roberto Serna-Blasco, Atocha Romero, Alberto Cruz-Bermúdez
Journal: The Lancet Oncology (2024)
Investing in the future of global health
Authors: Austen Davis, Samira Asma, Mark Blecher, Christoph Benn, Satoshi Ezoe, Helga Fogstad, Gargee Gosh, Gabriel Leung, Serena Ng, Justice Nonvignon, Olive Shisana, Viroj Tangcharoensathien, Juan Pablo Uribe, John-Arne Røttingen
Journal: The Lancet (2024)
Global health 2050: the path to halving premature death by mid-century
Authors: Dean T Jamison, Lawrence H Summers, Angela Y Chang, Omar Karlsson, Wenhui Mao, Ole F Norheim, Osondu Ogbuoji, Marco Schäferhoff, David Watkins, Olusoji Adeyi, George Alleyne, Ala Alwan, Shuchi Anand, Ruth Belachew, Seth F Berkley, Stefano M Bertozzi, Sarah Bolongaita, Donald Bundy, Flavia Bustreo, Marcia C Castro, Simiao Chen, Victoria Y Fan, Ayodamope Fawole, Richard Feachem, Lia Gebremedhin, Jayati Ghosh, Sue J Goldie, Eduardo Gonzalez-Pier, Yan Guo, Sanjeev Gupta, Prabhat Jha, Felicia Marie Knaul, Margaret E Kruk, Christoph Kurowski, Gordon G Liu, Saeda Makimoto, Awad Mataria, Rachel Nugent, Hitoshi Oshitani, Ariel Pablos-Mendez, Richard Peto, Neelam Sekhri Feachem, Srinath Reddy, Nisreen Salti, Helen Saxenian, Justina Seyi-Olajide, Agnes Soucat, Stéphane Verguet, Armand Zimmerman, Gavin Yamey
Journal: The Lancet (2024)
Clinical profile analysis of SARS-CoV-2 community infections during periods with omicron BA.2, BA.4/5, and XBB dominance in Hong Kong: a prospective cohort study
Authors: Yawei Wang, Hau Chi So, Nicole Ngai Yung Tsang, Siu Kan Kwok, Benjamin J Cowling, Gabriel M Leung, Dennis Kai Ming Ip
Journal: The Lancet Infectious Diseases (2024)
Genotypic and phenotypic characterisation of respiratory syncytial virus after nirsevimab breakthrough infections: a large, multicentre, observational, real-world study
Authors: Slim Fourati, Alawiya Reslan, Jérome Bourret, Jean-Sébastien Casalegno, Yannis Rahou, Lionel Chollet, Sylvie Pillet, Pauline Tremeaux, Nefert Candace Dossou, Elyanne Gault, Maud Salmona, Berthe-Marie Imbert-Marcille, Audrey Mirand, Sylvie Larrat, Alice Moisan, Stéphane Marot, Aurélie Schnuriger, Nicolas Veyrenche, Ilka Engelmann, Lynda Handala, Amandine Henry, Valentin Stephan, Ségolène Brichler, Véronique Avettand-Fenoel, Nael Zemali, Caroline Lefeuvre, Charlotte Pronier, Luc Deroche, Marie-Christine Jaffar-Bandjee, Lina Mouna, Catherine Francois, Alexandre Regueme, Cédric Hartard, Sylvie Rogez, Floriane Gallais, Arnaud Ly, Christophe Rodriguez, Georges Dos Santos, Etienne Simon-Loriere, Olivier Schwartz, Julian Buchrieser, Jean-MiIchel Pawlotsky, Frédéric Lemoine, Etienne Audureau, Marie-Anne Rameix-Welti
Journal: The Lancet Infectious Diseases (2024)
Induction chemotherapy followed by standard chemoradiotherapy versus standard chemoradiotherapy alone in patients with locally advanced cervical cancer (GCIG INTERLACE): an international, multicentre, randomised phase 3 trial
Authors: Mary McCormack, Gemma Eminowicz, Dolores Gallardo, Patricia Diez, Laura Farrelly, Christopher Kent, Emma Hudson, Miguel Panades, Tony Mathew, Anjana Anand, Mojca Persic, Jennifer Forrest, Rajanee Bhana, Nicholas Reed, Anne Drake, Madhavi Adusumalli, Asima Mukhopadhyay, Margaret King, Karen Whitmarsh, John McGrane, Nicoletta Colombo, Choi Mak, Ranajit Mandal, Rahul Roy Chowdhury, Gabriela Alamilla-Garcia, Adriana Chávez-Blanco, Hilary Stobart, Amanda Feeney, Simran Vaja, Anne-Marie Hacker, Allan Hackshaw, Jonathan Andrew Ledermann
Journal: The Lancet (2024)
A validated heart-specific model for splice-disrupting variants in childhood heart disease
Authors: Robert Lesurf, Jeroen Breckpot, Jade Bouwmeester, Nour Hanafi, Anjali Jain, Yijing Liang, Tanya Papaz, Jane Lougheed, Tapas Mondal, Mahmoud Alsalehi, Luis Altamirano-Diaz, Erwin Oechslin, Enrique Audain, Gregor Dombrowsky, Alex V. Postma, Odilia I. Woudstra, Berto J. Bouma, Marc-Phillip Hitz, Connie R. Bezzina, Gillian M. Blue, David S. Winlaw, Seema Mital
Journal: Genome Medicine (2024)

Congenital heart disease (CHD) is the most common congenital anomaly. Almost 90% of isolated cases have an unexplained genetic etiology after clinical testing. Non-canonical splice variants that disrupt mRNA splicing through the loss or creation of exon boundaries are not routinely captured and/or evaluated by standard clinical genetic tests. Recent computational algorithms such as SpliceAI have shown an ability to predict such variants, but are not specific to cardiac-expressed genes and transcriptional isoforms.
Combinational regenerative inductive effect of bio-adhesive hybrid hydrogels conjugated with hiPSC-derived myofibers and its derived EVs for volumetric muscle regeneration
Authors: Jiseong Kim, Myung Chul Lee, Jieun Jeon, Alejandra Rodríguez-delaRosa, Yori Endo, Da-Seul Kim, Andrea Donaxi Madrigal-Salazar, Jeong Wook Seo, Hyeseon Lee, Ki-Tae Kim, Jae-I Moon, Seung Gwa Park, Mariana Carolina Lopez-Pacheco, Abdulhameed F Alkhateeb, Nebras Sobahi, Nicole Bassous, Wenpeng Liu, Jae Seo Lee, Seongsoo Kim, Dilara Yilmaz Aykut, Mahmoud Lotfi Nasr, Mohammad Asif Hussain, Soo-Hong Lee, Woo-Jin Kim, Olivier Pourquié, Indranil Sinha, Su Ryon Shin
Journal: Bioactive Materials (2024)
First step to environmentally sustainable endoscopy practice: Prospective study of minimizing multiple device use during screening colonoscopy at a large tertiary center
Authors: Prateek S. Harne, Vaishali Harne, Asad Rehman, Nirav Thosani, Madhav Desai
Journal: Endoscopy (2024)

Abstract Background The healthcare sector generates 8% of greenhouse gas emissions in the USA, of which gastrointestinal (GI) endoscopy is the third largest contributor. Single-use tools are a major contributor to modifiable waste generation during GI endoscopy. Through a quality improvement initiative, we aimed to reduce endoscopy waste by urging gastroenterologists to be mindful of tools used during polypectomies by avoiding using multiple tools. Methods We discussed green endoscopy initiatives in monthly journal club and business meetings. Over 14 weeks, 210 patients were included in the pre-intervention group and 112 in the post-intervention group. Results At baseline, 34% of colonoscopies required no intervention, 32% required one tool (either biopsy forceps or a snare), and 33% required multiple tools. After the intervention, the use of just one tool increased (17 percentage point increase; P=0.003) and the use of multiple tools decreased significantly (16 percentage point decrease; P=0.002). The odds ratio for use of a single tool compared with multiple tools after the intervention was 3.0 (95%CI 1.6 to 5.5; P=0.005). Conclusion This single-center quality improvement study noted a significant change in practice patterns favoring the use of a single tool over multiple tools during colonoscopies after an environmentally conscious practice intervention was applied. This intervention can be readily applied to reduce endoscopy-related waste.
Pathogenesis of Germinal Matrix Hemorrhage: Insights from Single-Cell Transcriptomics
Authors: Jiapei Chen, Jennifer Ja-Yoon Choi, Pin-Yeh Lin, Eric J. Huang
Journal: Annual Review of Pathology Mechanisms of Disease (2024)

The germinal matrix harbors neurogenic niches in the subpallium of the prenatal human brain that produce abundant GABAergic neurons. In preterm infants, the germinal matrix is particularly vulnerable to developing hemorrhage, which disrupts neurogenesis and causes severe neurodevelopmental sequelae. However, the disease mechanisms that promote germinal matrix hemorrhage remain unclear. Here, we review recent advances using single-cell transcriptomics to uncover novel mechanisms that govern neurogenesis and angiogenesis in the germinal matrix of the prenatal human brain. These approaches also reveal the critical role of immune–vascular interaction that promotes vascular morphogenesis in the germinal matrix and how proinflammatory factors from activated neutrophils and monocytes can disrupt this process, leading to hemorrhage. Collectively, these results reveal fundamental disease mechanisms and therapeutic interventions for germinal matrix hemorrhage.
Intratumoral STING agonist reverses immune evasion in PD-(L)1-refractory Merkel cell carcinoma: mechanistic insights from detailed biomarker analyses
Authors: Thomas Pulliam, Saumya Jani, Peter H Goff, Rashmi Bhakuni, Shira Tabachnick-Cherny, Kimberly Smythe, Brandon W Seaton, Lisa Tachiki, Rima Kulikauskas, Candice Church, David M Koelle, Paul Nghiem, Shailender Bhatia
Journal: Journal for ImmunoTherapy of Cancer (2024)

Antibodies blocking programmed death (PD)-1 or its ligand (PD-L1) have revolutionized cancer care, but many patients do not experience durable benefits. Novel treatments to stimulate antitumor immunity are needed in the PD-(L)1 refractory setting. The stimulator of interferon genes (STING) protein, an innate sensor of cytoplasmic DNA, is a promising target with several agonists in development. However, response rates in most recent clinical trials have been low and mechanisms of response remain unclear. We report detailed biomarker analyses in a patient with anti-PD-L1 refractory, Merkel cell polyomavirus (MCPyV)-positive, metastatic Merkel cell carcinoma (MCC) who was treated with an intratumoral (IT) STING agonist (ADU-S100) plus intravenous anti-PD-1 antibody (spartalizumab) and experienced a durable objective response with regression of both injected and non-injected lesions.