This twice-monthly newsletter highlights recently published research where Dana-Farber faculty are listed as first or senior authors. The information is pulled from PubMed and this issue notes papers published from July 1 through July 15.
If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know by emailing [email protected].
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Blood
Large-Scale Dependency and Drug Screens to Characterize the Therapeutic Vulnerabilities of Multiple Myeloma with 1q
Sklavenitis-Pistofidis R, Lightbody ED, Reidy M, Tsuji J, Alberge JB, Aranha MP, Heilpern-Mallory D, Roweth HG, Huynh D, Chong SJF, Chung AY, Zhang J, Hackett L, Haradhvala NJ, Wu T, Su NK, Berrios B, Belkin S, Dutta AK, Davids MS, Getz G, Ghobrial IM
The development of targeted therapy for patients with multiple myeloma (MM) is hampered by the low frequency of actionable genetic abnormalities. Gain or amplification of chromosome 1q (1q+) is the most frequent arm-level copy number gain in patients with MM and is associated with higher risk of progression and death despite recent therapeutic advances. Thus, developing targeted therapy for patients with MM with 1q+ stands to benefit a large portion of patients in need of more effective management. Here, we used large-scale dependency screens and drug screens to systematically characterize the therapeutic vulnerabilities of MM with 1q+ and displayed increased sensitivity to myeloid cell leukemia-1 (MCL1) and phosphatidyl inositol 3-kinase (PI3K) inhibitors. Using single-cell RNA sequencing, we compared subclones with and without 1q+ within the same patient tumors and demonstrated that 1q+ is associated with higher levels of MCL1 and the PI3K pathway. Furthermore, by isolating isogenic clones with different copy number profiles for part of the chromosome 1q arm, we observed increased sensitivity to MCL1 and PI3K inhibitors with arm-level gain. Lastly, we demonstrated synergy between MCL1 and PI3K inhibitors and dissected their mechanism of action in MM with 1q+, uncovering a cytostatic effect. In conclusion, this study highlights that MM with 1q+ may present enhanced sensitivity to MCL1 and PI3K inhibitors, enabling their use at lower doses without sacrificing efficacy, and may thus accelerate the development of targeted therapy for patients with MM and 1q+.
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Blood
Loss of BCL7A Permits IRF4 Transcriptional Activity and Cellular Growth in Multiple Myeloma
Chakraborty C, Talluri S, Binder M, JE, Derebail S, Samur AA, Epstein C, Anderson KC, Shammas M, Samur MK, Fulciniti M, Munshi NC
Multiple myeloma (MM) is a complex hematological malignancy characterized by genomic changes and transcriptomic dysregulation. Initial exome sequencing approaches have failed to identify any single, frequent (>25%) mutation in the coding genome. However, using whole-genome sequencing, we found that one of the genomic regions most frequently mutated (62% of the patients with MM) was the 5' untranslated region and/or intron 1 of the BCL7A gene. RNA-sequencing data from a large cohort suggest a loss of BCL7A expression in a large majority of patients with MM as compared with normal plasma cells. BCL7A loss of function in a panel of MM cell lines led to a highly proliferative phenotype in vitro and in vivo, whereas its ectopic expression significantly reduced cell viability, suggesting a tumor suppressor function for BCL7A in MM. We studied the cellular and molecular effects of BCL7A loss and observed that it endows myeloma cells with proliferative potential in cooperation with the plasma cell-defining transcription factor IRF4. BCL7A is involved in a direct protein-protein interaction with IRF4, limiting its DNA-binding activity. Loss of BCL7A thus enhances the expression of IRF4-associated cytokines and reduces mitochondrial metabolism and reactive oxygen species levels. Our study therefore suggests that BCL7A loss provides the necessary molecular change to allow IRF4-mediated transcriptional activity and MM cell growth and survival.
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Cancer Discovery
Requirement for Cyclin D1 Underlies Cell-Autonomous HIF2 Dependence in Kidney Cancer
Shirole NH, Kesar D, Lee Y, Goodale A, Syamala S, Kukreja S, Li R, Qiu X, Yu W, Goldman S, Cejas P, Long HW, Adelman K, Doench JG, Sellers WR, Kaelin WG Jr
Inactivation of the VHL gene stabilizes HIF2α, which drives clear-cell renal cell carcinoma (ccRCC). The HIF2α inhibitor belzutifan is approved for ccRCC treatment, but de novo and acquired resistance are common. HIF2α, bound to ARNT, transcriptionally activates many genes. We performed CRISPR-mediated gene activation screens in HIF2α-dependent ccRCC lines treated with a belzutifan analog to identify HIF2α-responsive genes that confer cell-autonomous belzutifan resistance when not downregulated. Sustaining the expression of the HIF2α target gene CCND1, encoding cyclin D1, promoted HIF2α independence/belzutifan resistance. This activity requires CDK4/6 activation by cyclin D1 but is not solely due to phosphorylation of the canonical cyclin D1 target, pRB. Indeed, ccRCC lines lacking all three pRB family members remained at least partially HIF2α-dependent. In this context, however, a kinase-defective cyclin D1 variant partially overrode belzutifan's antiproliferative effects, suggesting that ccRCC promotion by cyclin D1 requires the phosphorylation of pRB paralogs and one or more kinase-independent cyclin D1 activities.
SIGNIFICANCE: We discovered that cyclin D1 is the key target of HIF2 driving the cell-autonomous proliferation of VHL-mutant kidney cancers and that cyclin D1 has targets beyond pRB in this setting. These findings have implications for treating kidney cancer with HIF2 inhibitors, alone or in combination with CDK4/6 inhibitors.
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Cancer Discovery
The Future of Personalized Cancer Vaccines
Martini DJ, Wu CJ
In early clinical studies, genomics-guided personalized cancer vaccines (PCV) have demonstrated the capabilities of inducing long-term, tumor-specific immune responses across various malignancies, clinical settings, and treatment regimens. Now that PCVs have advanced to large-scale, randomized clinical trials, we are at a pivotal time. The future success of PCVs will likely be dictated by our collective ability to apply and iterate upon the foundational lessons from early and ongoing in-depth studies so that we can rationally exploit the cytolytic capabilities of PCVs to eradicate advanced cancer, cure patients in the adjuvant setting, and prevent the development of malignancy in high-risk patients.
SIGNIFICANCE: The advent of modern next-generation sequencing and innovative clinical bioinformatics platforms have fueled the development of genomics-guided PCVs targeting neoantigens. As we anticipate the results of several pivotal randomized clinical trials investigating PCVs across solid tumors, collaborative efforts are warranted to apply insights from first-generation trials to leverage the capabilities of PCVs to reduce cancer-associated morbidity and mortality across the spectrum of oncological care.
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New England Journal of Medicine
Neoadjuvant and Adjuvant Pembrolizumab in Locally Advanced Head and Neck Cancer
Uppaluri R, Haddad RI
BACKGROUND: The benefit of the addition of perioperative pembrolizumab to standard care with surgery and adjuvant therapy for patients with locally advanced head and neck squamous-cell carcinoma (HNSCC) is unclear.
METHODS: In this phase 3, open-label trial, we randomly assigned participants with locally advanced HNSCC in a 1:1 ratio to receive 2 cycles of neoadjuvant pembrolizumab and 15 cycles of adjuvant pembrolizumab (both at a dose of 200 mg every 3 weeks) in addition to standard care (pembrolizumab group) or standard care alone (control group). Standard care was surgery and adjuvant radiotherapy with or without concomitant cisplatin. The primary end point was event-free survival, sequentially assessed in participants whose tumors expressed programmed death ligand 1 (PD-L1) with a combined positive score (CPS) of 10 or more (CPS-10 population), participants whose tumors expressed PD-L1 with a CPS of 1 or more (CPS-1 population), and all the participants. A higher CPS indicates a higher proportion of cells that express PD-L1.
RESULTS: A total of 363 participants (234 with a CPS of ≥10 and 347 with a CPS of ≥1) were assigned to the pembrolizumab group and 351 (231 with a CPS of ≥10 and 335 with a CPS of ≥1) to the control group. Surgery was completed in approximately 88% of the participants in each group. At the first interim analysis, the median follow-up was 38.3 months. Event-free survival at 36 months was 59.8% in the pembrolizumab group and 45.9% in the control group (hazard ratio for progression, recurrence, or death, 0.66; 95% confidence interval [CI], 0.49 to 0.88; two-sided P = 0.004) in the CPS-10 population; 58.2% and 44.9%, respectively (hazard ratio, 0.70; 95% CI, 0.55 to 0.89; two-sided P = 0.003), in the CPS-1 population; and 57.6% and 46.4%, respectively (hazard ratio, 0.73; 95% CI, 0.58 to 0.92; two-sided P = 0.008), in the total population. Grade 3 or higher treatment-related adverse events occurred in 44.6% of the participants in the pembrolizumab group and in 42.9% of those in the control group, including death in 1.1% and 0.3%, respectively. Potentially immune-mediated adverse events of grade 3 or higher occurred in 10.0% of the participants in the pembrolizumab group.
CONCLUSIONS: The addition of neoadjuvant and adjuvant pembrolizumab to standard care significantly improved event-free survival among participants with locally advanced HNSCC. Neoadjuvant pembrolizumab did not affect the likelihood of surgical completion. No new safety signals were identified. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; KEYNOTE-689 ClinicalTrials.gov number, NCT03765918.).
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Cell
A Multi-Adjuvant Personal Neoantigen Vaccine Generates Potent Immunity in Melanoma
Blass E, Keskin DB, Tu CR, Forman C, Vanasse A, Sax HE, Shim B, Chea V, Kim N, Carulli I, Southard J, Lyu H, Lu W, Rickles-Young M, Afeyan AB, Olive O, Mehndiratta A, Greenslade H, Shetty K, Baginska J, Gomez Diaz I, Nau A, Pfaff KL, Gans A, Ranasinghe S, Buchbinder EI, Sussman TA, Insco ML, Yoon CH, Rodig SJ, Shukla SA, Li S, Aster JC, Braun DA, Cibulskis C, Hacohen N, Neuberg DS, Giobbie-Hurder A, Livak KJ, Fritsch EF, Oliveira G, Simon JM, Wu CJ, Ott PA
Personalized neoantigen-targeting vaccines have demonstrated great promise; however, improved immunogenicity is still needed. Since antigen availability and effective T cell priming are critical for maximal immunogenicity, we tested a synthetic long peptide vaccine formulated with Montanide, poly-ICLC, and locally administered ipilimumab in addition to systemic nivolumab in 10 patients with melanoma. These personalized vaccines generated de novo ex vivo T cell responses against the majority of immunizing neoepitopes in all 9 fully vaccinated patients and ex vivo CD8+ T cell responses in 6 of 9. Vaccination induced hundreds of circulating and intratumoral T cell receptor (TCR) clonotypes that were distinct from those arising after PD-1 inhibition. By linking the vaccine neoantigen specificity of T cell clonotypes with single-cell phenotypes in tumors, we demonstrate remodeling of the intratumoral T cell repertoire following vaccination. These observations show that multi-pronged immune adjuvanticity can boost T cell responses to neoantigen-targeting vaccines.
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Journal of Clinical Oncology
Stereotactic Radiosurgery in Patients with Small Cell Lung Cancer and 1-10 Brain Metastases: A Multi-Institutional, Phase II, Prospective Clinical Trial
Aizer AA, Tanguturi SK, Shi DD, Catalano PJ, Shin KY, Ricca I, Johnson M, Benham G, Kozono DE, Mak RH, Hertan L, Chipidza F, Krishnan M, Pashtan I, Peng L, Qian JM, Shiloh RY, Sands J, Wen PY, Haas-Kogan DA, Rahman R
PURPOSE: Stereotactic radiation (SRS/SRT) as opposed to whole-brain radiation (WBRT) represents the standard of care for patients with a limited number of brain metastases given the relatively favorable toxicity profile associated with stereotactic treatment. However, in patients with small cell lung cancer (SCLC), WBRT remains standard because of a lack of prospective data supporting SRS/SRT and concerns related to intracranial progression and neurologic death when WBRT is omitted. We conducted a single-arm, multicenter, phase II trial of SRS/SRT in patients with SCLC and 1-10 brain metastases to assess neurologic death rates relative to historical controls managed with WBRT (ClinicalTrials.gov identifier: NCT03391362).
METHODS: Patients were eligible if they had SCLC or an extrathoracic small cell primary and 1-10 brain metastases. Previous brain-directed radiation including prophylactic cranial irradiation was not permitted. Neurologic death was defined as marked, progressive, radiographic brain progression accompanied by corresponding neurologic symptomatology without systemic disease progression or systemic symptoms of a life-threatening nature. Close imaging-based surveillance of the brain post-SRS/SRT was used.
RESULTS: Between February 2018 and April 2023, 100 patients were enrolled. The median number of brain metastases was 2 (IQR, 1-4; range, 1-10). The median overall survival was 10.2 months; only 22% of patients required salvage WBRT. In total, 20 neurologic deaths were observed, relative to 64 non-neurologic deaths. The neurologic death rate at 1 year was 11.0% (95% CI, 5.8 to 18.1); the historical rate in patients managed with WBRT was 17.5%.
CONCLUSION: Our prospective, multi-institutional study demonstrated low rates of neurologic death when SRS/SRT as opposed to WBRT is used in patients with SCLC and 1-10 brain metastases who are surveilled closely post-treatment, supporting the utility of stereotactic approaches in this population.
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Journal of Clinical Oncology
Tumor-Intrinsic and Microenvironmental Determinants of Impaired Antitumor Immunity in Chromophobe Renal Cell Carcinoma
Labaki C, Saad E, Hobeika C, Bi K, Alchoueiry M, Camp S, Matar S, El Ahmar N, Priolo C, Khabibullin D, Salem S, Pimenta E, Park J, Eid M, Semaan K, Fu J, Denize T, El Hajj Chehade R, Machaalani M, Nawfal R, Khatoun WD, Saleh M, El Masri J, Xu W, McGregor BA, Hirsch MS, Xie W, McDermott DF, Signoretti S, Van Allen EM, Choueiri TK, Henske EP
PURPOSE: While immune checkpoint inhibition (ICI) has transformed the management of many advanced renal cell carcinomas (RCCs), the determinants of effective antitumor immunity for chromophobe RCC (ChRCC) and renal oncocytic tumors remain an unmet clinical and scientific need.
METHODS: Single-cell transcriptomic and T-cell receptor profiling was performed on tumor and adjacent normal tissue of patients with ChRCC and renal oncocytic neoplasms. Using machine learning, the cellular origin of renal oncocytic neoplasms was evaluated, with analysis of associated oncogenic pathways. Using immunohistochemistry, immune infiltration was analyzed in renal oncocytic neoplasms in comparison with clear cell RCC (ccRCC). Immune checkpoint expression, clonal expansion, and tumor specificity were compared between ChRCC and ccRCC. Using the International Metastatic RCC Database Consortium data set, clinical outcomes of patients with metastatic ChRCC (mChRCC) treated with first-line systemic regimens were compared with those of patients with ccRCC.
RESULTS: We validated α-intercalated cells as the cellular origin of renal oncocytic neoplasms. We identified a downregulation of HLA class I molecules with enrichment of potentially targetable pathways including mammalian target of rapamycin and ferroptosis in ChRCC. The tumor microenvironment of ChRCC showed markedly decreased immune infiltration, with a pronounced depletion in tumor-infiltrating CD8+ T cells. ChRCC-infiltrating CD8+ T cells demonstrated lower immune checkpoint expression, diminished clonal expansion, and decreased tumor specificity. Clinical analysis identified poor survival outcomes selectively among patients with mChRCC treated with immune-based therapies.
CONCLUSION: Immunogenomic analysis of ChRCC revealed profound depletion of T cells, with an immune phenotype marked by a lack of expression of immune checkpoints and poor tumor specificity, suggesting that the few T cells in these tumor types are likely nonspecific bystanders. This immune-cold environment hinders an effective response to immunotherapy and underscores the need for ChRCC-tailored treatments designed to improve tumor-specific T-cell infiltration into the microenvironment.
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Journal of the National Cancer Institute
Rising Incidence of Early-Onset Colorectal Cancer: Impact of Anatomy and Histology
Char SK, Chan JA, Ng K
The incidence of early-onset colorectal cancer (EO-CRC)—defined as CRC diagnosed in adults younger than age 50—has been steadily increasing over the past several decades. Although the steepest rise has been seen among adults aged 20-29 years, EO-CRC incidence is highest in adults aged 45-49 years, with an age-adjusted incidence rate of 33.4 per 100 000 between 2015 and 2019. EO-CRC is currently the leading cause of cancer-related death in men age <50 years and the second leading cause among women age <50 years. In response to these trends, the United States Preventative Services Task Force (USPSTF) formally recommended lowering the age at which to start CRC screening from 50 to 45 years for average-risk individuals in 2021.
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Molecular Cell
Cellular Metabolite Sensors: Arginine? It's in the Bag!
Jackson TD, Palozzi JM, Puigserver P
In this issue of Molecular Cell, Chen et al.1 identify a novel arginine-sensing system, composed of the cytosolic proteins BAG2 and SAMD4B, which promotes cancer cell survival during arginine deficiency.
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Molecular Cell
Structural Basis for the Midnolin-Proteasome Pathway and Its Role in Suppressing Myeloma
Nardone C, Gao J, Seo HS, Mintseris J, Ort L, Yip MCJ, Negasi M, Besschetnova AK, Kamitaki N, Gygi SP, Dhe-Paganon S, Munshi NC, Fulciniti M, Greenberg ME, Shao S, Elledge SJ, Gu X
The midnolin-proteasome pathway degrades many nuclear proteins without ubiquitination, but how it operates mechanistically remains unclear. Here, we present structures of the midnolin-proteasome complex, revealing how established proteasomal components are repurposed to enable a unique form of proteolysis. While the proteasomal subunit PSMD2/Rpn1 binds to ubiquitinated or ubiquitin-like (Ubl) proteins, we discover that it also interacts with the midnolin nuclear localization sequence, elucidating how midnolin's activity is confined to the nucleus. Likewise, PSMD14/Rpn11, an enzyme that normally cleaves ubiquitin chains, surprisingly functions non-enzymatically as a receptor for the midnolin Ubl domain, positioning the substrate-binding Catch domain directly above the proteasomal entry site to guide substrates into the proteasome. Moreover, we demonstrate that midnolin downregulation is critical for the survival of myeloma cells by stabilizing the transcription factor substrate IRF4. Our findings uncover the mechanisms underlying the midnolin-proteasome pathway and midnolin downregulation as a driver of multiple myeloma.
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Nature
A DNA-Gated Molecular Guard Controls Bacterial Hailong Anti-Phage Defence
Tan JMJ, Cofsky JC, Syangtan D, Hobbs SJ, Del Mármol J, Jost M, Kruse AC, Sorek R, Kranzusch PJ
Animal and bacterial cells use nucleotidyltransferase (NTase) enzymes to respond to viral infection and control major forms of immune signalling including cGAS-STING innate immunity and CBASS anti-phage defence1-4. Here we discover a family of bacterial defence systems, which we name Hailong, that use NTase enzymes to constitutively synthesize DNA signals and guard against phage infection. Hailong protein B (HalB) is an NTase that converts deoxy-ATP into single-stranded DNA oligomers. A series of X-ray crystal structures define a stepwise mechanism of HalB DNA synthesis initiated by a C-terminal tyrosine residue that enables de novo enzymatic priming. We show that HalB DNA signals bind to and repress activation of a partnering Hailong protein A (HalA) effector complex. A 2.0-Å cryo-electron microscopy structure of the HalA-DNA complex reveals a membrane protein with a conserved ion channel domain and a unique crown domain that binds the DNA signal and gates activation. Analysing Hailong defence in vivo, we demonstrate that viral DNA exonucleases required for phage replication trigger release of the primed HalA complex and induce protective host cell growth arrest. Our results explain how inhibitory nucleotide immune signals can serve as molecular guards against phage infection and expand the mechanisms NTase enzymes use to control antiviral immunity.
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Nature Communications
Intraindividual Epigenetic Heterogeneity Underlying Phenotypic Subtypes of Advanced Prostate Cancer
Mizuno K, Ku SY, Venkadakrishnan VB, Bakht MK, Presser AG, Kim MJ, Tewari AK, Long HW, Choueiri TK, Balk S, Hill S, Einstein D, Taplin ME, Beltran H
Castration-resistant prostate cancer is a heterogeneous disease with variable phenotypes commonly observed in later stages of the disease. These include cases that retain expression of luminal markers and those that lose hormone dependence and acquire neuroendocrine features. While there are distinct transcriptomic and epigenomic differences between castration-resistant adenocarcinoma and neuroendocrine prostate cancer, the extent of overlap and degree of diversity across tumor metastases in individual patients has not been fully characterized. Here we perform combined DNA methylation, RNA-sequencing, H3K27ac, and H3K27me3 profiling across metastatic lesions from patients with CRPC/NEPC. Integrative analyses identify DNA methylation-driven gene links based on location (H3K27ac, H3K27me3, promoters, gene bodies) pointing to mechanisms underlying dysregulation of genes involved in tumor lineage (ASCL1, AR) and therapeutic targets (PSMA, DLL3, STEAP1, B7-H3). Overall, these data highlight how integration of DNA methylation with RNA-sequencing and histone marks can inform intraindividual epigenetic heterogeneity and identify putative mechanisms driving transcriptional reprogramming in castration-resistant prostate cancer.
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Proceedings of the National Academy of Sciences of the U.S.A.
A Degradable Form of Polyoma Small T Antigen Reveals the High Specificity of TAZ in Regulating Gene Expression
Wang Y, Manokaran C, Huang K, Roberts TM
The study of DNA tumor viruses has revolutionized cancer biology, partly by virtue of the unique capabilities of viral oncoproteins to manipulate key proteins and pathways involved in tumorigenesis. We find a high affinity and selective binding of the polyoma small T antigen (PyST) with the transcription cofactor TAZ. By engineering a degradable version of PyST, we demonstrate that, when TAZ activity is modulated by PyST, a surprisingly small number of genes have altered expression and thus are candidate transcription targets of TAZ. Notably, knocking out TAZ, or its target genes CTGF or CYR61, abolishes the growth-promoting properties of PyST that are evident upon growth factor withdrawal. Therefore, by controlling the protein abundance of PyST and consequently TAZ activity, we find that TAZ is a transcriptional coactivator that can achieve important biological effects by acting on a limited number of gene targets.
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Science Immunology
The 10 Commandments of Immunoregulation in Lymphoma
de Los Reyes Capilla Guerra M, Griffin GK
Diffuse large B cell lymphoma (DLBCL) is a subtype of non-Hodgkin’s lymphoma that is characterized by a high risk of relapse. Therefore, identification of key modulators of disease progression and treatment resistance is imperative. In this study, Garcia-Lacarte et al. investigated the mechanisms underlying the ambiguous role of the immunomodulatory cytokine interleukin-10 (IL-10) in DLBCL. The authors observed up-regulation of the IL-10/STAT3 (signal transducer and activator of transcription 3) axis in DLBCL, particularly in the “ABC” subtype, and confirmed its association with B cell survival and the immune evasion marker PD-L1. Although these data suggested that IL-10 likely played an oncogenic role, genetic deletion of lymphoma-derived IL-10 in a mouse model of ABC-type DLBCL paradoxically increased disease severity. This suggested that the oncogenic effect of the IL-10/STAT3 axis on DLBCL cells could be counterbalanced by opposing effects on the microenvironment. Consistent with this, the authors showed that lymphoma-derived IL-10 maintained key effector populations in the microenvironment, such as dendritic cells and CD8+ T cells, and reduced suppressive cell types, such as regulatory T cells and macrophages, and angiogenesis-related gene expression programs.
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American Journal of Hematology
Regression of Monosomy 7 Clone in Patient with RECQL4-Associated Syndrome
Nunes SC, Reed HD, Pellin D, Harris C, Andresen F, Abu-El-Haija A, Barbera C, Schienda J, Madden JA, Bledsoe JR, Brundige K, Day-Lewis M, Nguyen AA, Shimamura A, Williams DA
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Annals of Surgical Oncology
ASO Visual Abstract: Impact of the American Society of Breast Surgeons' Guidelines on Genetic Testing and Contralateral Prophylactic Mastectomy Rates
Weiss A, Rosito MS, Braun D, Barton B, McGrath M, Stokes S, Laws A, Warren L, Morganti S, Lynce F, Bychkovsky B, Rana HQ, Davis D, Stopfer J, Garber JE, King TA
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Cancer Immunology Research
First-in-Human Clinical Trial of Vaccination with WDVAX, a Dendritic Cell-Activating Scaffold Incorporating Autologous Tumor Cell Lysate, in Patients with Metastatic Melanoma
Hodi FS, Giobbie-Hurder A, Adu-Berchie K, Ranasinghe S, Lako A, Severgnini M, Thrash EM, Weirather JL, Baginska J, Manos MP, Doherty EJ, Stafford A, Daley H, Ritz J, Ott PA, Pfaff KL, Rodig SJ, Yoon CH, Dranoff G, Mooney DJ
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Cell Reports Medicine
Immune Targeting of Triple-Negative Breast Cancer Through a Clinically Actionable STING Agonist-CAR T Cell Platform
Zhang Y, Li Z, Ritter J, Brea EJ, Mahadevan NR, Dillon DA, Park SR, Liu EM, Tolstorukov MY, McGourty WE, Lizotte P, Ivanova EV, Fahey C, Haratani K, Thai TC, Soroko KM, Kivlehan S, Smith EL, Gokhale PC, Paweletz CP, Barbie DA, Barbie TU
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Clinical Cancer Research
Clinicogenomic Characterization of Inflammatory Breast Cancer
Priedigkeit N, Harrison B, Shue R, Hughes ME, Li Y, Lebrón-Torres A, Kirkner GJ, Spurr LF, Remolano MC, Strauss S, Files J, Feeney AM, Grant L, Mohammed-Abreu A, Garrido-Castro A, Barroso-Sousa R, Bychkovsky B, Nakhlis F, Bellon JR, King TA, Winer EP, Lindeman N, Johnson BE, Sholl L, Dillon D, Overmoyer B, Tolaney SM, Cherniack AD, Lin NU, Lynce F
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Gastroenterology
Chemical Perturbations Impacting Histone Acetylation Govern Colorectal Cancer Differentiation
Likasitwatanakul P, Li Z, Doan P, Spisak S, Raghawan AK, Liu Q, Liow P, Lee S, Chen D, Bala P, Sahgal P, Aitymbayev D, Thalappillil JS, Papanastasiou M, Hawkins W, Carr SA, Park H, Cleary JM, Qi J, Sethi NS
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Gynecologic-Oncology
Phase 2, Two-Stage Study of Avelumab and Axitinib in Patients with Mismatch Repair Proficient Recurrent or Persistent Endometrial Cancer
Lee EK, Xiong N, Krasner C, Polak M, Campos S, Wright AA, Liu JF, Shea M, Yeku O, Castro C, Porter R, Stover EH, Koppermann L, Smith J, Sawyer H, Hayes M, Zhou N, Cheng SC, Bouberhan S, Pfaff KL, Rodig SJ, Jones S, Penson RT, Matulonis UA, Konstantinopoulos PA
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Journal of Pediatric Surgery
Prevalence, Characteristics, and Management of Pancreatic Tumors Among Children with Tuberous Sclerosis Complex
Li R, Miguel C, Schienda J, Arcasoy E, Kamihara J, Peters JM, Davis PE, Sahin M, Weil BR
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Leukemia and Lymphoma
A Phase-2 Study of Pembrolizumab in Patients with Biologically Selected Subtypes of Relapsed/Refractory Aggressive Lymphomas
Merrill MH, Redd RA, Fisher DC, Abramson JS, Barnes J, Jacobson CA, Kim AI, Jester HD, Jeter EL, McDonough MM, Armand P, Jacobsen ED
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NPJ Precision Oncology
Plasma Epigenomic Profiling Reveals Treatment-Emergent Squamous Transformation in Prostate Cancer
Semaan K, Nawfal R, Canniff J, Savignano H, Seo JH, Siegmund SE, Wu SJ, Rotow JK, Lee GM, El Hajj Chehade R, Zhang Z, Gulati GS, Phillips N, Lee GG, French CA, Hirsch MS, Jacene HA, Choudhury AD, Choueiri TK, Freedman ML, Baca SC, Berchuck JE
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