Dana-Farber Research News 05.15.2026
Welcome to Dana-Farber's Research News
May 15, 2026
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 April 16 - 30.
If you are a Dana-Farber faculty member and you think your paper is missing from Research News, please let us know by emailing dfciresearchnews@dfci.harvard.edu.
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Blood Wu CJ Remarkable progress in the understanding of disease pathogenesis and treatment across hematologic malignancies has been achieved in the past two decades. Nevertheless, the reliable elimination of disease remains elusive for many cancers. Chronic lymphocytic leukemia (CLL) exemplifies the needs that must be addressed to close the gap between discovery science and remaining clinical challenges. In CLL, targeted therapies have substantially prolonged survival and enabled long-term disease control for many patients. However, curative outcomes remain exceptional, particularly in high-risk groups such as those with TP53 disruption, dual resistance to BTK and BCL2 inhibitors, or transformation to aggressive lymphoma. Recent insights into the interconnection between cancer and immunity have positioned CLL as a model example of cancer-associated immunodeficiency-a realization brought into sharp focus by the SARS-CoV-2 pandemic where CLL patients were at extremely high-risk for infection and poor outcomes. Thus, complications related to infections, autoimmunity and secondary cancers continue to contribute substantially to morbidity and mortality, underscoring the need for research on immune dysfunction in CLL. Furthermore, pronounced heterogeneity in disease progression and therapeutic resistance highlight the need for mechanistic studies to clarify these distinct biological patterns. Advances in these areas not only hold the promise of curative therapy for broader patient subgroups in CLL but will also inform innovation in research on other cancers, particularly in establishing a molecular definition of disease and defining those interactions with the underlying and resultant immune deficiencies. |
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Cancer Cell Bui TM, Jimenez ER, Li Z, Foidart P, Puleo J, Yan P, Jhaveri A, Yang L, Nishida J, Seehawer M, Cai X, Parker KA, Sumer OE, Huang XY, Patel A, Dillon D, Dranoff G, Cristea S, Polyak K Immune escape during the ductal carcinoma in situ (DCIS)-to-invasive breast cancer (IBC) transition shapes tumor evolution. Through transcriptomic mapping of the immune landscapes of normal breast, DCIS, and IBC from large patient cohorts, we identified T and myeloid cells as the primary distinguishing features between DCIS and IBC. We discovered cycling regulatory T cells (cycTreg) as an orchestrator of immunosuppression in IBC. cycTreg frequency predicts cytotoxic CD8+, TCR diversity, disease-specific survival in IBC, and recurrence in DCIS. In a rat model of breast cancer, we demonstrated that cycTreg act as precursors to mature Treg and are inducible by tumor-localized type 2 dendritic cells. Profiling of tumors subjected to ?OX40 and ?PD-L1 therapies revealed an IL-33-mediated fibroblast-cycTreg signaling loop, the disruption of which enhances intratumoral antigen-experienced CD8+ effectors and systemic immunosurveillance. Our study defines cycTreg as critical inducers of immune escape and promising immuno-oncology targets in breast cancer. |
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Cancer Discovery Transposable Element Activation: A Hallmark of Cancer Burns KH Transposable elements (TEs), mobile DNA sequences that can move independently about the genome, make up about half of the human genome and are mostly silenced by epigenetic modifications in healthy differentiated cells. Global epigenetic dysregulation during oncogenic transformation causes TE expression, contributing to transcriptional rewiring and TE activity as insertional mutagens. TE nucleic acids are sensed in the cytoplasm, initiating inflammation that can be therapeutically manipulated to activate anti-tumor immune responses. Here we detail how TEs contribute to six of the classic hallmarks of cancer and propose widespread TE expression and activation as a new hallmark of cancer. |
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JAMA Oncology Healthy Lifestyle Advice and Practice Among Cancer Survivors in the US Cao C, Giovannucci EL, Lee IM, Partridge AH, Ligibel JA Since the 2010s, the American Society of Clinical Oncology, the American Cancer Society, and the American College of Sports Medicine have recommended incorporating lifestyle counseling into standard care across the cancer control continuum. Evidence indicates that behavioral counseling promotes lifestyle modifications in individuals with chronic conditions, but little is known about the receipt of lifestyle advice and ongoing lifestyle practices among cancer survivors. To address these knowledge gaps, we examined trends and cancer-specific patterns in receipt of lifestyle advice and ongoing lifestyle practices for weight control, physical activity (PA) or exercise, sodium or salt intake, and fat or energy intake among US cancer survivors and explored associations between receipt of lifestyle advice and engagement in corresponding lifestyle practices. |
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Journal of Clinical Oncology Haddad RI PURPOSE: The PD-1 inhibitor pembrolizumab is approved as first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). In LEAP-010 (ClinicalTrials.gov identifier: NCT04199104), the multikinase inhibitor lenvatinib plus pembrolizumab was evaluated as first-line therapy in participants with PD-L1 combined positive score (CPS) ?1 R/M HNSCC. METHODS: In this phase III, randomized, placebo-controlled, double-blind study, participants 18 years and older with PD-L1 CPS ?1 R/M HNSCC deemed incurable by local therapy were randomly assigned 1:1 to lenvatinib 20 mg plus pembrolizumab 200 mg IV once every 3 weeks for ?35 cycles or placebo orally once daily plus pembrolizumab 200 mg IV once every 3 weeks for ?35 cycles. Primary end points were objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Per the prespecified analysis plan, ORR and PFS were reported from the first interim analysis (IA1; data cutoff: July 6, 2022), and OS from IA2 (data cutoff: May 30, 2023). RESULTS: Five hundred eleven participants were randomly assigned to lenvatinib plus pembrolizumab (n = 256) or placebo plus pembrolizumab (n = 255). The median time from random assignment to data cutoff was 11.5 months for IA1 and 21.3 months for IA2. At IA1, the median PFS was 6.2 months for lenvatinib plus pembrolizumab versus 2.8 months for placebo plus pembrolizumab (hazard ratio [HR], 0.64 [95% CI, 0.50 to 0.81]; P = .0001040); the ORR was 46.1% versus 25.4%, respectively (difference = 20.2% [95% CI, 10.5 to 29.6]; P = .0000251). At IA2, the median OS was 15.0 months for lenvatinib plus pembrolizumab versus 17.9 months for placebo plus pembrolizumab (HR,1.15 [95% CI, 0.91 to 1.45]; P = .882). At IA2, 170 (66.9%) participants receiving lenvatinib plus pembrolizumab had grade 3-4 all-cause adverse events compared with 97 (38.3%) participants on placebo plus pembrolizumab. CONCLUSION: In participants with PD-L1 CPS ?1 R/M HNSCC, first-line lenvatinib plus pembrolizumab significantly improved ORR and PFS, but not OS, compared with placebo plus pembrolizumab. The safety profile was consistent with published data. |
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Journal of Clinical Oncology Cutler C, Kim HT, El Banna H, Halloran E, Matozel E, Ho VT, Koreth J, Gooptu M, Shapiro R, Kelkar A, Gibson C, Nikiforow S, Nageshwar P, Reynolds C, Ansuinelli M, Tamada R, Au C, Panaro K, Gervais C, DeFilipp Z, El-Jawahri A, Chen YB, Soiffer R, Antin JH, Ritz J PURPOSE: Chronic graft-versus-host disease (cGVHD) is a multisystem alloimmune disorder associated with abnormal B-cell biology and aberrant antibody responses. As B-cell-directed therapy can effectively treat established cGVHD, we tested whether prophylactic B-cell depletion could prevent the development of corticosteroid-requiring cGVHD following allogeneic transplantation. METHODS: We performed a randomized, placebo-controlled, and blinded trial comparing four doses of the B-cell-depleting antibody obinutuzumab (1,000 mg once on days 90, 180, 270, and 365 after transplantation) with placebo in transplant recipients receiving tacrolimus-based GVHD prevention at higher risk of cGVHD. The primary end point was the 1-year incidence of corticosteroid-requiring cGVHD. We measured antibody responses against Y chromosome-encoded minor histocompatibility (H-Y) antigens and correlated their occurrence with corticosteroid-requiring cGVHD incidence. RESULTS: One hundred seventy-eight participants were analyzed. The prophylactic administration of obinutuzumab resulted in profound B-cell depletion, a significant reduction in the incidence of steroid-requiring cGVHD at 1 year (13.3% v 35.2%; P = .0005), and an improvement in immunosuppression-free, relapse-free survival (48% v 34% at 2 years; P = .02). Neutropenia was more common in the obinutuzumab arm, but nonrelapse mortality was not different. In participants without preformed H-Y antibodies at the time of study intervention, obinutuzumab resulted in the most significant reduction in steroid-requiring cGVHD at 12 months (8.6%) compared with obinutuzumab participants with H-Y antibodies (40%) or placebo participants regardless of antibody status (41% with antibodies, 57% without antibodies). CONCLUSION: In allogeneic transplant recipients at higher risk of cGVHD, early B-cell depletion results in a significant reduction in the incidence of corticosteroid-requiring cGVHD. |
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Molecular Cell MRE11 Proximal Polyadenylation Site-Mediated Looping Impacts Transcription and Genomic Stability Huang K, Brault ME, Cong K, Azazmeh N, Lee S, Lantz GA, Raskind G, Beroukhim R, Chowdhury D Alternative polyadenylation (APA) generates transcript isoforms with variable 3' untranslated regions (UTR) lengths, yet its role in DNA damage response (DDR) genes is poorly understood. Here, we demonstrate that the proximal polyadenylation site (pPAS) of MRE11 engages in PAS-promoter looping to facilitate RNA polymerase recycling and sustain high promoter activity-a mechanism not well characterized in mammals. Deletion of the MRE11 pPAS disrupts this looping, reduces MRE11 transcription, impairs MRE11-RAD50-NBS1 (MRN) complex levels, and phenocopies hypomorphic MRE11 mutations. MRE11pPAS-/- cells exhibit ectopic DNA replication and reduced viability under overgrowth conditions. 5-ethynyl-2'-deoxyuridine sequencing (EdU-seq) revealed aberrant DNA synthesis occurring primarily at intronic and intergenic regions, where MRE11 chromatin immunoprecipitation sequencing (ChIP-seq) showed decreased binding correlating with elevated replication. Furthermore, multiple DDR genes with several PASs also form PAS-promoter loops, suggesting a broader regulatory mechanism. Together these findings identify the MRE11 pPAS as a critical noncoding element that maintains genome stability through transcriptional regulation via PAS-promoter looping. |
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Nature Communications Face Aging Rate Quantifies Change in Biological Age to Predict Cancer Outcomes Haugg F, Lee G, He J, Warrington A, Bontempi D, Bitterman DS, Catalano PJ, Prudente V, Pai S, Guthier C, Kann BH, Aerts HJ, Mak RH Chronological age predicts cancer survival but does not capture differences in biological aging rates. We apply FaceAge, an artificial intelligence algorithm that predicts biological age from a facial photograph, to serial clinical facial photographs to calculate the Face Aging Rate (FAR; change in FaceAge divided by the time between photographs). We analyze data from 2276 cancer patients receiving radiation therapy, using photographs captured during routine care. Higher FAR is associated with worse overall survival in stratified analyses of cohorts with the following intervals between photographs: short 10-365 days (adjusted hazard ratio [aHR] and 95% confidence interval: 1.25 [1.03-1.51]), mid 366-730 days (aHR: 1.37 [1.00-1.86]), and long 731-1,460 days (aHR: 1.65 [1.22-2.22]) after adjustment for time between photographs, sex, race, and diagnosis. FAR provides additional prognostic information beyond single time-point measures of FaceAge. FAR is a non-invasive prognostic biomarker that captures dynamic changes in biological aging. |
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Nature Communications Structural Basis of QueC-Family Protein Function in qatABCD Anti-Phage Defense Gao A, Wassarman DR, Kranzusch PJ QueC proteins are nucleoside biosynthesis enzymes required for production of the 7-deazaguanine derivative queuosine. Recently, QueC-family proteins were also shown to catalyze a deazaguanylation protein-nucleobase conjugation reaction in type IV CBASS bacterial anti-phage defense. Here we determine the structural basis of QueC-family protein function in a distinct bacterial immunity system named qatABCD. We demonstrate that the Pseudomonas aeruginosa QueC-family protein QatC forms a specific complex with the immunity protein QatB and that this complex is minimally required for qatABCD defense. Crystal structures of the QatBC complex enable direct comparison of qatABCD and type IV CBASS defense and support a shared role for QueC-family proteins in targeting protein substrates for N-terminal modification. We show that the QatB unstructured N-terminus and N-terminal glycine motif are essential for qatABCD defense in vivo, suggesting a modification occurs analogous to CBASS deazaguanylation. These findings highlight broad roles of QueC proteins beyond nucleoside biosynthesis and suggest that adaptation of QueC-like proteins for specialized biochemical functions is a common strategy in bacterial anti-phage immunity. |
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Nature Medicine Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma: The CAR-PRISM Phase 2 Trial Nadeem O, Cordas Dos Santos DM, Nikiforow S, Bosch-Vilaseca A, O'Donnell E, Redd R, Sperling AS, Liu Y, McEntire C, Arters F, O'Donnell C, Kineavy B, Marto M, Bergeron A, Swenson E, McHugh K, Caron A, Berry Q, Wei H, Durlacher E, Grimm E, Corrado F, Bidikian N, Gervais C, Panaro K, Smith EL, Anderson K, Jacobson C, Munshi NC, Richardson P, Trippa L, Ritz J, Ghobrial IM High-risk smoldering multiple myeloma (HR-SMM) carries an increased risk of progression to multiple myeloma, making it an ideal setting to test whether chimeric antigen receptor (CAR) T cell therapy can achieve curative outcomes. Here in this phase 2 study, patients with HR-SMM received ciltacabtagene autoleucel (cilta-cel) at 0.3-0.5?×?106 or >0.5?×?106 viable CAR+ T cells per kilogram without induction or bridging therapy. Patients with >40% marrow involvement were excluded. Primary endpoints were dose-limiting toxicities (DLTs) and treatment-emergent adverse events; secondary endpoints included response and minimal residual disease (MRD) negativity. As of 11 February 2026, 20 patients had been treated. The trial met the prespecified endpoints. No DLTs occurred. Adverse events included transient cytopenias (90% grade 3/4) and cytokine release syndrome (100% grade 1/2). Non-immune effector cell-associated neurotoxicity syndrome neurologic toxicities (NINTs) occurred in seven patients, with four comprising cranial nerve palsies that completely resolved. Three patients had persistent grade 1 symptoms. At a median follow-up of 15.3?months, all patients achieved MRD negativity 10-6 by 2?months and have remained MRD negative. Sixteen patients with follow-up >6?months achieved a complete response; no progression or deaths were observed. Cilta-cel produced rapid, deep, sustained MRD-negative responses in HR-SMM without induction therapy. Toxicities were consistent with the safety profile of cilta-cel. ClinicalTrials.gov: NCT05767359. |
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Nature Medicine Uncovering Risk Factors in the Exposome for Early-Onset Colorectal Cancer Lee DJ, Baca S, Ng K The exposome encompasses the totality of environmental exposures encountered by an individual from conception onward. First proposed in 2005 by Christopher Wild and later refined by Wild to include internal (for example, metabolism and epigenetics), specific external (for example, diet and pollutants) and general external (for example, socioeconomic status) domains, the exposome has provided a useful framework for investigating causes of the alarming rise in early-onset colorectal cancer (CRC) — that is, CRC diagnosed in individuals aged below 50 years. In this issue of Nature Medicine, Maas et al. utilize epigenetic markers as molecular fingerprints of the exposome to evaluate established and novel risk factors of early-onset CRC. They identified picloram — a herbicide first registered in the USA in 1964 and later classified by the US Environmental Protection Agency as a restricted-use pesticide in 1978 — as a potential driver of this disease, but many questions remain. |
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ACS Applied Materials and Interfaces Validation of DoriVac (DNA Origami Vaccine) Efficacy in a Metastatic Melanoma Model Rajwar A, Dembele H, Graveline AR, Vernet A, Sanchez M, Bardales S, Shih WM, Zeng YC |
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ACS Chemical Biology O'Donohue E, Haigis KM |
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Advanced Science Kochs T, Nath P, Chen A, Romee R, Maia A |
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Blood Advances Aguirre LE, Kim HT, Frumm SM, Kelkar AH, Ho V, Gooptu M, Koreth J, Shapiro RM, Romee R, Nikiforow S, Antin JH, Soiffer RJ, Shimony S, Luskin MR, Garcia JS, Chen EC, Wadleigh M, Winer ES, Stone RM, DeAngelo DJ, Cutler CS, Stahl M |
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Blood Advances Shimony S, Murdock HM, Keating J, Tsai HK, Sasi A, Gibson CJ, Reilly CR, Neuberg D, Stone RM, Lindsley RC |
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Blood Cancer Discovery CAR-NK Cells in B-Cell Lymphoma: A New Frontier toward Accessible and Scalable Cellular Therapy Duléry R, Romee R |
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Cancer Epidemiology, Biomarkers, and Prevention Kauffman TL, O'Donnell EK, Marinac CR, Babic A, Adams K, Beckwith JB, Berman TA, Brantley KD, Chowdhury D, Crompton BD, Diller LR, Feltmate CM, Florez N, Garber JE, Ghobrial I, Hanna GJ, Hormoz S, Kamihara J, Mittendorf EA, Partridge AH, Rodriguez NJ, Sands J, Thapa B, Weeks LD, Woo SB, Yurgelun MB, Parmigiani G, Rebbeck TR, Syngal S |
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Cell Chemical Biology Degrading TBK1 to Disarm VHL-Deficient Renal Cancer Kwon H, Bers AE, Barbie DA |
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Cell Reports Medicine Yeo YY, Qiu H, Chang Y, Yiu SPT, Yeung J, Michel HA, Wang Y, Wang Y, Wu W, Wright K, Shaban M, Sadigh S, Shanmugam V, Cramer P, Paczkowska J, Stephan P, Liao G, Huang AY, Wang H, Mitra B, Gewurz BE, Zhao B, Zhang B, Shalek AK, Mahmood F, Chiarle R, Shipp MA, Rodig SJ, Jiang S |
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Clinical Cancer Research Jänne PA |
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Environmental Pollution Ugai S, Mizuno H, Matsuda K, Kondo A, Zhong Y, Nakazawa N, Miyahara S, Väyrynen SA, Chan AT, Song M, Giannakis M, Meyerhardt JA, Väyrynen JP, Nowak JA, Ogino S, Ugai T |
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Expert Opinion on Investigational Drugs Liu Y, Mo C, Midha S, Hartley-Brown M, Nadeem O, Nicholson T, Salman TJ, Laubach J, Richardson PG |
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Haematologica DuMontier C, Cronin AM, Hshieh TT, Sanyal A, DeAngelo DJ, Munshi NC, Stone RM, Soiffer RJ, Driver JA, Abel GA |
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JCI Insight Lobo M, Bahar F, Schnabel JL, Shetty A, Khaddour K, Thakuria M, Silk AW, DeCaprio JA |
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JCO Oncology Practice Sentana-Lledo D, Rami A, Zhong C, Xie W, Tchitchkan E, Stoltenberg H, Wolanski A, Ritzer J, Jacene H, Ravi P |
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Journal of Cancer Education Berry JL, O'Loughlin L, Barnum K, Drews RE, Freed JA, Patell R, Rangachari D |
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Journal of Clinical Sleep Medicine Li A, Petishnok LC, Epstein SF, Walsh ML, Gauvreau K, Klerman EB, Ng AK, Chen MH |
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Journal of General Internal Medicine Volandes AE, Chang Y, Lindvall C, Samarakoon U, Hashimoto T, Shirai N, Paasche-Orlow GA, Sciacca K, Walker-Corkery B, El-Jawahri A, Barry MJ, Joel M, Durieux BN, Kwok A, Ouchi K |
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Journal of Geriatric Oncology Agaronnik ND, Davis J, Sounack T, Keating NL, Lindvall C |
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Journal of Immunotherapy Cohen JV, Liu M, Rogers G, Manos M, McHugh P, Schwer A, Ott PA, Silk AW, Khaddour K, Buchbinder EI, Gibson WJ, Hodi FS Jr, Tsibris HC |
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Journal of Nuclear Medicine Choueiri TK |
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Journal of Palliative Medicine Kwok A, Sciacca K, Ljungberg BF, Samineni S, Tulsky JA, Lindvall C, Gray TF |
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Journal of Palliative Medicine Agaronnik ND, Davis J, Sounack T, Manz CR, Lindvall C |
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Journal of the American Chemical Society Li C, Munshi NC |
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Journal of the American Society of Nephrology Chewcharat A, Anumolu R, Suresh A, Yamada KS, Ortega JL, Mehta AK, Zargari KM, Rubman MB, Alikhan FM, DeFilipp Z, Chowdhury RB, Jacobson CA, Nadeem O, Soiffer RJ, Leaf DE, Sise ME, Romee R, Shapiro R, Gupta S |
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Journal of Thoracic Oncology Brunetti L, Santo V, Pecci F, Rotow J, Adib E, Ricciuti B, Aerts HJWL, Cortellini A |
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Nature Reviews Cancer Context-Dependent Synthetic Lethality - An Emerging Precision Therapeutic Approach Chang L, Shaw K, Vazquez F, Sellers WR |
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Nature Reviews Clinical Oncology The Clinical Landscape of HIF2? Inhibitors in Oncology Saad E, Machaalani M, McDermott DF, Choueiri TK |
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Nature Microbiology Ragucci AE, Antine SP, Leviss EM, Mooney SE, Garcia JM, Lee ASY, Kranzusch PJ |
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NPJ Precision Oncology Yang DD, Rickles-Young M, Tsuji J, Cibulskis C, Fleharty M, Reardon B, Park J, Van Allen EM, Choudhury AD |
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Oral Oncology Bakhtiar M, Al-Inaya Y, Das D, Margalit DN, Tishler RB, Haddad RI, Hanna GJ, Rettig EM, Faden DL, Schoenfeld JD |
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Pediatric Blood and Cancer Lung Adenocarcinoma and Genetic Cancer Predisposition in an Adolescent Neel DS, Chu D, Jimenez-Kurlander L, Vargas SO, Perkins R, Collins NB |
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Proceedings of the Royal Society Population-Scale Long-Read DNA Sequencing: Peering Under the Hood of the New Evolutionary Genomics Edwards SV, Li H |
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Scientific Reports Kim H, Cazaubiel J, Chiang TL, Stylianakis D, Fitzgerald S, De Silva P, Gurjao C, Giannakis M |
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Thrombosis Research Perrone O, Tarhini N, Duzan J, Vrooman LM, Burns M, Kumar R |
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Transplantation and Cellular Therapy Takahashi T, Wachter F, Keating AK |
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Transplantation and Cellular Therapy Pozo-Kaderman C, Miran DM, Keane EP, Amonoo HL |