tbuckley/cabot-search huggingface dataset:
Targeting the tumor mutanome for personalized vaccination in a TMB low non-small cell lung cancer
Authors: Katy McCann, Adrian von Witzleben, Jaya Thomas, Chuan Wang, Oliver Wood, Divya Singh, Konstantinos Boukas, Kaidre Bendjama, Nathalie Silvestre, Finn Cilius Nielsen, Gareth Thomas, Tilman Sanchez-Elsner, Jason Greenbaum, Stephen Schoenberger, Bjoern Peters, Pandurangan Vijayanand, Natalia Savelyeva, Christian Ottensmeier
Journal: Journal for ImmunoTherapy of Cancer (2022)

Background Cancer is characterized by an accumulation of somatic mutations, of which a significant subset can generate cancer-specific neoepitopes that are recognized by autologous T cells. Such neoepitopes are emerging as important targets for cancer immunotherapy, including personalized cancer vaccination strategies. Methods We used whole-exome and RNA sequencing analysis to identify potential neoantigens for a patient with non-small cell lung cancer. Thereafter, we assessed the autologous T-cell reactivity to the candidate neoantigens using a long peptide approach in a cultured interferon gamma ELISpot and tracked the neoantigen-specific T-cells in the tumor by T-cell receptor (TCR) sequencing. In parallel, identified gene variants were incorporated into a Modified Vaccinia Ankara-based vaccine, which was evaluated in the human leucocyte antigen A*0201 transgenic mouse model (HHD). Results Sequencing revealed a tumor with a low mutational burden: 2219 sequence variants were identified from the primary tumor, of which 23 were expressed in the transcriptome, involving 18 gene products. We could demonstrate spontaneous T-cell responses to 5/18 (28%) mutated gene variants, and further analysis of the TCR repertoire of neoantigen-specific CD4 + and CD8 + T cells revealed TCR clonotypes that were expanded in both blood and tumor tissue. Following vaccination of HHD mice, de novo T-cell responses were generated to 4/18 (22%) mutated gene variants; T cells reactive against two variants were also evident in the autologous setting. Subsequently, we determined the major histocompatibility complex restriction of the T-cell responses and used in silico prediction tools to determine the likely neoepitopes. Conclusions Our study demonstrates the feasibility of efficiently identifying tumor-specific neoantigens that can be targeted by vaccination in tumors with a low mutational burden, promising successful clinical exploitation, with trials currently underway.
45P Alofanib in subsequent therapy of advanced gastric cancer: Final results from the phase Ib clinical trial
Authors: L.Y. Vladimirova, V. Kurakin, N. Besova, G. Statsenko, A. Mochalova, N. Trenina, E. Artamonova, K. Novoselova, T. Titova, N.A. Abramova, E. Obarevich, A. Kashanova, M. Suetina, I. Agranov, S. Iugai, G. Raskin, V. Kazey, I. Rykov, S. Tjulandin, I. Tsimafeyeu
Journal: Annals of Oncology (2022)
IMPACT OF HEREDITARY THROMBOPHILIAS ON OUTCOMES IN HOSPITALIZED PATIENTS WITH STEMI
Authors: Omar Khdeir, Adnan Humam Hajjar, Aysheh Khdeir, Fatima Khdeir, Sreeram Yalamanchili, Ramtej Atluri, Satyam Krishan
Journal: Journal of the American College of Cardiology (2022)
A Boost for Muscle with Gene Therapy
Authors: Jeffrey S. Chamberlain
Journal: New England Journal of Medicine (2022)

Gene therapy for disorders affecting muscle, such as Duchenne's muscular dystrophy and myotubular myopathy, has been challenging, in large part owing to the difficulty of delivering the therapeutic gene to cells within the mass of muscle tissue. A recent study of the adeno-associated virus capsid provides a candidate vector for targeting muscle cells.
Use of At-Home COVID-19 Tests — United States, August 23, 2021–March 12, 2022
Authors: Benjamin Rader, Autumn Gertz, A. Danielle Iuliano, Matthew Gilmer, Laura Wronski, Christina M. Astley, Kara Sewalk, Tanner J. Varrelman, Jon Cohen, Rishika Parikh, Heather E. Reese, Carrie Reed, John S. Brownstein
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

COVID-19 testing provides information regarding exposure and transmission risks, guides preventative measures (e.g., if and when to start and end isolation and quarantine), identifies opportunities for appropriate treatments, and helps assess disease prevalence (1). At-home rapid COVID-19 antigen tests (at-home tests) are a convenient and accessible alternative to laboratory-based diagnostic nucleic acid amplification tests (NAATs) for SARS-CoV-2, the virus that causes COVID-19 (2-4). With the emergence of the SARS-CoV-2 B.1.617.2 (Delta) and B.1.1.529 (Omicron) variants in 2021, demand for at-home tests increased
5MO Comprehensive dose-finding strategy for single-agent RP-3500, a highly selective inhibitor of ataxia telangiectasia and Rad3-related (ATR) kinase
Authors: E. Fontana, E. Lee, E. Rosen, D. Spigel, M. Højgaard, S. Lheureux, N.B. Mettu, L. Carter, R. Plummer, P. Manley, D. Ulanet, V. Rimkunas, I.M. Silverman, J. O'Connell, R. McDougall, M. Wainszelbaum, Y. Xu, M. Koehler, A.J. Fretland, T.A. Yap
Journal: Annals of Oncology (2022)
Neoadjuvant in situ vaccination with cowpea mosaic virus as a novel therapy against canine inflammatory mammary cancer
Authors: Daniel Alonso-Miguel, Guillermo Valdivia, Diego Guerrera, Maria Dolores Perez-Alenza, Stanislav Pantelyushin, Angela Alonso-Diez, Veronique Beiss, Steven Fiering, Nicole F Steinmetz, Maria Suarez-Redondo, Johannes vom Berg, Laura Peña, Hugo Arias-Pulido
Journal: Journal for ImmunoTherapy of Cancer (2022)

Inflammatory mammary cancer (IMC), the counterpart of human inflammatory breast cancer (IBC), is the deadliest form of canine mammary tumors. IMC patients lack specific therapy and have poor outcomes. This proof-of-principle preclinical study evaluated the efficacy, safety, and effect on survival of neoadjuvant intratumoral (in situ) empty cowpea mosaic virus (eCPMV) immunotherapy in companion dogs diagnosed with IMC.Ten IMC-bearing dogs were enrolled in the study. Five dogs received medical therapy, and five received weekly neoadjuvant in situ eCPMV immunotherapy (0.2-0.4 mg per injection) and medical therapy after the second eCPMV injection. Efficacy was evaluated by reduction of tumor growth; safety by hematological and biochemistry changes in blood and plasma; and patient outcome by survival analysis. eCPMV-induced immune changes in blood cells were analyzed by flow cytometry; changes in the tumor microenvironment were evaluated by CD3 (T lymphocytes), CD20 (B lymphocytes), FoxP3 (Treg lymphocytes), myeloperoxidase (MPO; neutrophils), Ki-67 (proliferation index, PI; tumor cell proliferation), and Cleaved Caspase-3 (CC-3; apoptosis) immunohistochemistry.Two neoadjuvant in situ eCPMV injections resulted in tumor shrinkage in all patients by day 14 without systemic adverse events. Although surgery for IMC is generally not an option, reduction in tumor size allowed surgery in two IMC patients. In peripheral blood, in situ eCPMV immunotherapy was associated with a significant decrease of Treg+/CD8+ ratio and changes in CD8+Granzyme B+ T cells, which behave as a lagging predictive biomarker. In the TME, higher neutrophilic infiltration and MPO expression, lower tumor Ki-67 PI, increase in CD3+ lymphocytes, decrease in FoxP3+/CD3+ ratio (p<0.04 for all comparisons), and no changes in CC-3+ immunostainings were observed in post-treatment tumor tissues when compared with pretreatment tumor samples. eCPMV-treated IMC patients had a statistically significant (p=0.033) improved overall survival than patients treated with medical therapy.Neoadjuvant in situ eCPMV immunotherapy demonstrated anti-tumor efficacy and improved survival in IMC patients without systemic adverse effects. eCPMV-induced changes in immune cells point to neutrophils as a driver of immune response. Neoadjuvant in situ eCPMV immunotherapy could be a groundbreaking immunotherapy for canine IMC and a potential future immunotherapy for human IBC patients.
CARDIAC MR PATTERNS OF ISCHEMIC INJURY AND INFARCTION AND RELATIONSHIP WITH CORONARY CULPRIT LESIONS IN WOMEN WITH MINOCA (MI WITH NON-OBSTRUCTIVE CORONARY ARTERIES)
Authors: Harmony R. Reynolds, Julia Huang, Tara Sedlak, Akiko Maehara, Nathaniel Rosso Smilowitz, Ehtisham Mahmud, Janet Wei, Michael J. Attubato, Bobby Heydari, Caitlin McAneny Giesler, Mitsuaki Matsumura, Anais Hausvater, Judith S. Hochman, Raymond Y. Kwong
Journal: Journal of the American College of Cardiology (2022)
EFFECTS OF SACUBITRIL/VALSARTAN VERSUS VALSARTAN ON RENAL FUNCTION IN PATIENTS WITH TYPE 2 DIABETES AND HEART FAILURE WITH PRESERVED EJECTION FRACTION: PARAGON-HF
Authors: Alexander Peikert, Muthiah Vaduganathan, Finnian McCausland, Brian Claggett, Safia Chatur, Milton Packer, Marc A. Pfeffer, Faiez Zannad, Martin Lefkowitz, Burkert Mathias Pieske, Hans-Dirk Düngen, John J.V. McMurray, Scott D. Solomon
Journal: Journal of the American College of Cardiology (2022)
CAUSES AND PREDICTORS OF 90-DAY READMISSION AFTER IMPLANTABLE CARDIOVERTER DEFIBRILLATOR (ICD)- AN ANALYSIS OF THENATIONWIDE READMISSIONS DATABASE (NRD)
Authors: Mukunthan Murthi, Sujitha Velagapudi, Bharosa Sharma, Prajwal Shrestha, Hafeez Shaka
Journal: Journal of the American College of Cardiology (2022)
Autoantibodies against interleukin-1 receptor antagonist in multisystem inflammatory syndrome in children: a multicentre, retrospective, cohort study
Authors: Jochen Pfeifer, Bernhard Thurner, Christoph Kessel, Natalie Fadle, Parastoo Kheiroddin, Evi Regitz, Marie-Christin Hoffmann, Igor Age Kos, Klaus-Dieter Preuss, Yvan Fischer, Klaus Roemer, Stefan Lohse, Kristina Heyne, Marie-Claire Detemple, Michael Fedlmeier, Hendrik Juenger, Harald Sauer, Sascha Meyer, Tilman Rohrer, Helmut Wittkowski, Sören L Becker, Katja Masjosthusmann, Robert Bals, Stephan Gerling, Sigrun Smola, Moritz Bewarder, Einat Birk, Andre Keren, Michael Böhm, André Jakob, Hashim Abdul-Khaliq, Jordi Anton, Michael Kabesch, Rosa Maria Pino-Ramirez, Dirk Foell, Lorenz Thurner
Journal: The Lancet Rheumatology (2022)
Bcl-xL Enforces a Slow-Cycling State Necessary for Survival in the Nutrient-Deprived Microenvironment of Pancreatic Cancer
Authors: Yogev Sela, Jinyang Li, Shivahamy Maheswaran, Robert Norgard, Salina Yuan, Maimon Hubbi, Miriam Doepner, Jimmy P. Xu, Elaine S. Ho, Clementina Mesaros, Colin Sheehan, Grace Croley, Alexander Muir, Ian A. Blair, Ophir Shalem, Chi V. Dang, Ben Z. Stanger
Journal: Cancer Research (2022)

Abstract Solid tumors possess heterogeneous metabolic microenvironments where oxygen and nutrient availability are plentiful (fertile regions) or scarce (arid regions). While cancer cells residing in fertile regions proliferate rapidly, most cancer cells in vivo reside in arid regions and exhibit a slow-cycling state that renders them chemoresistant. Here, we developed an in vitro system enabling systematic comparison between these populations via transcriptome analysis, metabolomic profiling, and whole-genome CRISPR screening. Metabolic deprivation led to pronounced transcriptional and metabolic reprogramming, resulting in decreased anabolic activities and distinct vulnerabilities. Reductions in anabolic, energy-consuming activities, particularly cell proliferation, were not simply byproducts of the metabolic challenge, but rather essential adaptations. Mechanistically, Bcl-xL played a central role in the adaptation to nutrient and oxygen deprivation. In this setting, Bcl-xL protected quiescent cells from the lethal effects of cell-cycle entry in the absence of adequate nutrients. Moreover, inhibition of Bcl-xL combined with traditional chemotherapy had a synergistic antitumor effect that targeted cycling cells. Bcl-xL expression was strongly associated with poor patient survival despite being confined to the slow-cycling fraction of human pancreatic cancer cells. These findings provide a rationale for combining traditional cancer therapies that target rapidly cycling cells with those that target quiescent, chemoresistant cells associated with nutrient and oxygen deprivation. Significance: The majority of pancreatic cancer cells inhabit nutrient- and oxygen-poor tumor regions and require Bcl-xL for their survival, providing a compelling antitumor metabolic strategy.
Site of Alcohol First-Pass Metabolism Among Women
Authors: Neda Seyedsadjadi, M. Belen Acevedo, Raul Alfaro, Vijay A. Ramchandani, Martin H. Plawecki, Blair Rowitz, Marta Yanina Pepino
Journal: JAMA Network Open (2022)

a Subsets of participants matched on Tmax to control for gastric emptying time.b Data on alcohol pharmacokinetics from a subsample of these SG participants
EVOLUTION AND SUSTAINABILITY OF CARDIO-ONCOLOGY PROGRAMS IN LOW-INCOME NATIONS
Authors: Laura Gomez, Pamela Piña Santana, Lina Colon, Elizabeth Leon, Sergio Badillo, Miguel Delgado, Humberto Gomez, Gismeily Pringle, Janissa Holguin, Seledonia Martinez, Amparo Taveras, Santiago Collado, Cesar J. Herrera, Centros de Diagnostico
Journal: Journal of the American College of Cardiology (2022)
Clinical, radiological and pathological findings in patients with persistent lung disease following SARS-CoV-2 infection
Authors: Claudia Ravaglia, Claudio Doglioni, Marco Chilosi, Sara Piciucchi, Alessandra Dubini, Giulio Rossi, Federica Pedica, Silvia Puglisi, Luca Donati, Sara Tomassetti, Venerino Poletti
Journal: European Respiratory Journal (2022)

Some patients experience pulmonary sequelae after SARS-CoV-2 infection, ranging from self-limited abnormalities to major lung diseases. Morphological analysis of lung tissue may help our understanding of pathogenic mechanisms and help to provide consistent personalised management. The aim of this study was to ascertain morphological and immunomolecular features of lung tissue. Transbronchial lung cryobiopsy was carried out in patients with persistent symptoms and computed tomography suggestive of residual lung disease after recovery from SARS-CoV-2 infection. 164 patients were referred for suspected pulmonary sequelae after COVID-19; 10 patients with >5% parenchymal lung disease underwent lung biopsy. The histological pattern of lung disease was not homogeneous and three different case clusters could be identified, which was mirrored by their clinical and radiological features. Cluster 1 ("chronic fibrosing") was characterised by post-infection progression of pre-existing interstitial pneumonias. Cluster 2 ("acute/subacute injury") was characterised by different types and grades of lung injury, ranging from organising pneumonia and fibrosing nonspecific interstitial pneumonia to diffuse alveolar damage. Cluster 3 ("vascular changes") was characterised by diffuse vascular increase, dilatation and distortion (capillaries and venules) within otherwise normal parenchyma. Clusters 2 and 3 had immunophenotypical changes similar to those observed in early/mild COVID-19 pneumonias (abnormal expression of STAT3 in hyperplastic pneumocytes and PD-L1, IDO and STAT3 in endothelial cells). This is the first study correlating histological/immunohistochemical patterns with clinical and radiological pictures of patients with post-COVID lung disease. Different phenotypes with potentially different underlying pathogenic mechanisms have been identified.
Identification of the estrogen receptor beta as a possible new tamoxifen-sensitive target in diffuse large B-cell lymphoma
Authors: Myra Langendonk, Mathilde R. W. de Jong, Nienke Smit, Jonas Seiler, Bart Reitsma, Emanuele Ammatuna, Andor W. J. M. Glaudemans, Anke van den Berg, Gerwin A. Huls, Lydia Visser, Tom van Meerten
Journal: Blood Cancer Journal (2022)

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma subtype. Despite the proven efficacy of combined immunochemotherapy (R-CHOP) in the majority of patients, ~40% of DLBCL patients do not respond or will relapse and consequently have a very poor prognosis. The development of targeted therapies has not improved patient survival, underscoring the need for new treatment approaches. Using an unbiased genome-wide CD20 guilt-by-association approach in more than 1800 DLBCL patients, we previously identified the estrogen receptor beta (ERβ) as a new target in DLBCL. Here, we demonstrate that ERβ is expressed at significantly higher levels in DLBCL compared to normal B cells, and ERβ plays a role in the protection against apoptosis in DLBCL. Targeting of the ERβ with the selective estrogen receptor modulator tamoxifen reduces cell viability in all tested DLBCL cell lines. Tamoxifen-induced cell death was significantly decreased in an ERβ knock-out cell line. The activity of tamoxifen was confirmed in a xenograft human lymphoma model, as tumor growth decreased, and survival significantly improved. Finally, tamoxifen-treated breast cancer (BC) patients showed a significantly reduced risk of 38% for DLBCL compared to BC patients who did not receive tamoxifen. Our findings provide a rationale to investigate tamoxifen, a hormonal drug with a good safety profile, in DLBCL patients.
Association of Genetic Ancestry With Terminal Duct Lobular Unit Involution Among Healthy Women
Authors: Hyuna Sung, Hela Koka, Natascia Marino, Ruth M Pfeiffer, Renata Cora, Jonine D Figueroa, Mark E Sherman, Gretchen L Gierach, Xiaohong R Yang
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Reduced age-related terminal duct lobular unit (TDLU) involution has been linked to increased breast cancer risk and triple-negative breast cancer. Associations of TDLU involution levels with race and ethnicity remain incompletely explored. Herein, we examined the association between genetic ancestry and TDLU involution in normal breast tissue donated by 2014 healthy women in the United States. Women of African ancestry were more likely than European women to have increased TDLU counts (odds ratio [OR]trend = 1.36, 95% confidence interval [CI] = 1.07 to 1.74), acini counts per TDLU (OR = 1.47, 95% CI = 1.06 to 2.03), and median TDLU span (ORtrend = 1.44, 95% CI = 1.08 to 1.91), indicating lower involution, whereas East Asian descendants were associated with decreased TDLU counts (ORtrend = 0.52, 95% CI = 0.35 to 0.78) after controlling for potential confounders. These associations are consistent with the racial variations in incidence rates of triple-negative breast cancer in the United States and suggest opportunities for future work examining whether TDLU involution may mediate the racial differences in subtype-specific breast cancer risk.
COMPARING VOLUME VERSUS QUALITY THRESHOLDS ON OUTCOMES AND ACCESS TO TRANSCATHETER AORTIC VALVE REPLACEMENT (TAVR) IN THE UNITED STATES: INSIGHTS FROM THE TVT REGISTRY
Authors: Adam J. Nelson, Zachary Wegermann, Dianne Gallup, Sean O’Brien, Andrzej Kosinski, Vinod H. Thourani, Dharam J. Kumbhani, Ajay J. Kirtane, Joe Allen, John D. Carroll, David M. Shahian, Nimesh Desai, Ralph G. Brindis, Eric D. Peterson, David Cohen, Sreekanth Vemulapalli
Journal: Journal of the American College of Cardiology (2022)
The current toolbox for APOBEC drug discovery
Authors: Michael J. Grillo, Katherine F.M. Jones, Michael A. Carpenter, Reuben S. Harris, Daniel A. Harki
Journal: Trends in Pharmacological Sciences (2022)

Mutational processes driving genome evolution and heterogeneity contribute to immune evasion and therapy resistance in viral infections and cancer. APOBEC3 (A3) enzymes promote such mutations by catalyzing the deamination of cytosines to uracils in single-stranded DNA. Chemical inhibition of A3 enzymes may yield an antimutation therapeutic strategy to improve the durability of current drug therapies that are prone to resistance mutations. A3 small-molecule drug discovery efforts to date have been restricted to a single high-throughput biochemical activity assay; however, the arsenal of discovery assays has significantly expanded in recent years. The assays used to study A3 enzymes are reviewed here with an eye towards their potential for small-molecule discovery efforts.
Cystic Fibrosis Transmembrane Conductance Regulator: Roles in Chronic Obstructive Pulmonary Disease
Authors: Mark Dransfield, Steven Rowe, Claus F. Vogelmeier, Jadwiga Wedzicha, Gerard J. Criner, MeiLan K. Han, Fernando J. Martinez, Peter Calverley
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Chronic obstructive pulmonary disease (COPD) manifests with a variety of clinical presentations, reflecting its complex pathology. Currently, care focuses on symptom amelioration and prevention of complications and thus is generally tailored to disease severity rather than targeting specific pathophysiologic mechanisms. Chronic inflammation and mucus hypersecretion are key features of COPD. Epithelial ion channel dysfunction may be important, as it results in airway dehydration and defective host defense, contributing to chronic airway inflammation. Recent evidence suggests considerable similarities between COPD and cystic fibrosis (CF), a disease in which chloride ion channel dysfunction has been extensively studied (in particular CFTR [CF transmembrane conductance regulator]). Understanding commonalities between CF and COPD, and the role of CFTR in CF, may help in designing strategies targeting ion channel dysfunction and lead to new treatments with potential to alter the natural history of disease progression. Here, we review the roles of airway mucus and CFTR in normal lung function, the previously underestimated contribution of mucus stasis to the development of COPD, and the evidence for targeting CFTR to counteract mucus accumulation.
BALLOON PULMONARY ANGIOPLASTY IN GROUP IV PH ASSOCIATED WITH INHERITED RED BLOOD CELL DYSCRASIAS
Authors: Naima Maqsood, Vladimir Lakhter, Estefania Oliveros Soles, Paul Forfia, William R. Auger, Riyaz Bashir, Anjali Vaidya
Journal: Journal of the American College of Cardiology (2022)
Macrophages use apoptotic cell-derived methionine and DNMT3A during efferocytosis to promote tissue resolution
Authors: Patrick B. Ampomah, Bishuang Cai, Santosh R. Sukka, Brennan D. Gerlach, Arif Yurdagul, Xiaobo Wang, George Kuriakose, Lancia N. F. Darville, Yan Sun, Simone Sidoli, John M. Koomen, Alan R. Tall, Ira Tabas
Journal: Nature Metabolism (2022)
Frailty, Guideline-Directed Medical Therapy, and Outcomes in HFrEF
Authors: Muhammad Shahzeb Khan, Matthew W Segar, Muhammad Shariq Usman, Sumitabh Singh, Stephen J Greene, Gregg C Fonarow, Stefan D Anker, G Michael Felker, James L Januzzi, Javed Butler, Ambarish Pandey
Journal: JACC Heart Failure (2022)
IMPACT OF RENIN-ANGIOTENSIN SYSTEM INHIBITORS ON MORTALITY DURING THE COVID PANDEMIC AMONG DIABETIC PATIENTS WITH STEMI UNDERGOING MECHANICAL REPERFUSION: INSIGHT FROM AN INTERNATIONAL STEMI REGISTRY
Authors: Giuseppe De Luca, Matteo Nardin, Magdy Algowhary, Berat Uguz, Dinaldo Cavalcanti Oliveira, Vladimir Ganyukov, Zan Dimitar Zimbakov, Miha Cercek, Lisette Okkels Jensen, Poay Huan Loh, Lucian Calmac, Gerard Roura, Alexandre Schaan Quadros, Marek Milewski, Fortunato Scotto di Uccio, Clemens von Birgelen, Gustavo Pessah, Bernardino Tuccillo, Giuliana Cortese, Guido Parodi, Mohammed Bouragdha, Elvin Kedhi, Pablo Lamelas, Harry Suryapranata, Monica Verdoia
Journal: Journal of the American College of Cardiology (2022)
The changing role of natural killer cells in cancer metastasis
Authors: Isaac S. Chan, Andrew J. Ewald
Journal: Journal of Clinical Investigation (2022)

Natural killer (NK) cells are innate immune cells that are critical to the body's antitumor and antimetastatic defense. As such, novel therapies are being developed to utilize NK cells as part of a next generation of immunotherapies to treat patients with metastatic disease. Therefore, it is essential for us to examine how metastatic cancer cells and NK cells interact with each other throughout the metastatic cascade. In this Review, we highlight the recent body of work that has begun to answer these questions. We explore how the unique biology of cancer cells at each stage of metastasis alters fundamental NK cell biology, including how cancer cells can evade immunosurveillance and co-opt NK cells into cells that promote metastasis. We also discuss the translational potential of this knowledge.