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1. Low PD-L1 expression, MAP2K2 alterations, and enriched HPV gene signatures characterize brain metastases in head and neck squamous cell carcinoma.

Author

Dennis, Michael, Pavlick, Dean, Kacew, Alec, Wotman, Michael, MacConaill, Laura, Jones, Stephanie, Pfaff, Kathleen, Rodig, Scott, Eacker, Stephen, Malig, Maika, Reister, Emily, Piccioni, David, Kesari, Santosh, Sehgal, Kartik, Haddad, Robert, Cohen, Ezra, Posner, Marshall, Deichaite, Ida, and Hanna, Glenn

Subjects
Brain metastasis, HPV, Head and neck cancer, Head and neck squamous cell carcinoma, Human papillomavirus, MAP2K2, Molecular, Next-generation sequencing, PD-L1, TSC1, Humans, Male, Middle Aged, Female, B7-H1 Antigen, Squamous Cell Carcinoma of Head and Neck, Brain Neoplasms, Aged, Head and Neck Neoplasms, Papillomaviridae, Adult, Gene Expression Regulation, Neoplastic, Mutation
Abstract

BACKGROUND: Brain metastasis (BM) is a rare but severe complication of head and neck squamous cell carcinoma (HNSCC), with limited knowledge of molecular characteristics and immunogenicity. METHODS: We analyzed 61 cases of HNSCC-BM from three academic institutions (n = 24) and Foundation Medicine Inc (FMI, n = 37). A subset of cases underwent next-generation sequencing, multiple immunofluorescence, and proximity ligation sequencing. Gene enrichment analysis compared alterations in FMI BM samples (n = 37) with local samples (n = 4082). RESULTS: Demographics included: median age of 59 years, 75% male, 55% current/former smokers, 75% oropharyngeal primary, and 67% human papillomavirus (HPV) +. ATM (54%), KMT2A (54%), PTEN (46%), RB1 (46%), and TP53 (46%) were frequently altered in BM samples from academic centers (62% HPV/p16+). Structural rearrangements ranged from 9 to 90 variants by proximity ligation sequencing. BMs had low densities of CD8+, PD-1+, PD-L1+, and FOXP3 + cells, and 92% had PD-L1 combined positive scores

Published
2024

2. A multidimensional analysis reveals distinct immune phenotypes and the composition of immune aggregates in pediatric acute myeloid leukemia

Author

Koedijk, Joost B., van der Werf, Inge, Penter, Livius, Vermeulen, Marijn A., Barneh, Farnaz, Perzolli, Alicia, Meesters-Ensing, Joyce I., Metselaar, Dennis S., Margaritis, Thanasis, Fiocco, Marta, de Groot-Kruseman, Hester A., Moeniralam, Rubina, Bang Christensen, Kristina, Porter, Billie, Pfaff, Kathleen, Garcia, Jacqueline S., Rodig, Scott J., Wu, Catherine J., Hasle, Henrik, Nierkens, Stefan, Belderbos, Mirjam E., Zwaan, C. Michel, and Heidenreich, Olaf

Published
2024
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3. A multi-modal single-cell and spatial expression map of metastatic breast cancer biopsies across clinicopathological features

Author

Klughammer, Johanna, Abravanel, Daniel L., Segerstolpe, Åsa, Blosser, Timothy R., Goltsev, Yury, Cui, Yi, Goodwin, Daniel R., Sinha, Anubhav, Ashenberg, Orr, Slyper, Michal, Vigneau, Sébastien, Jané‐Valbuena, Judit, Alon, Shahar, Caraccio, Chiara, Chen, Judy, Cohen, Ofir, Cullen, Nicole, DelloStritto, Laura K., Dionne, Danielle, Files, Janet, Frangieh, Allison, Helvie, Karla, Hughes, Melissa E., Inga, Stephanie, Kanodia, Abhay, Lako, Ana, MacKichan, Colin, Mages, Simon, Moriel, Noa, Murray, Evan, Napolitano, Sara, Nguyen, Kyleen, Nitzan, Mor, Ortiz, Rebecca, Patel, Miraj, Pfaff, Kathleen L., Porter, Caroline B. M., Rotem, Asaf, Strauss, Sarah, Strasser, Robert, Thorner, Aaron R., Turner, Madison, Wakiro, Isaac, Waldman, Julia, Wu, Jingyi, Gómez Tejeda Zañudo, Jorge, Zhang, Diane, Lin, Nancy U., Tolaney, Sara M., Winer, Eric P., Boyden, Edward S., Chen, Fei, Nolan, Garry P., Rodig, Scott J., Zhuang, Xiaowei, Rozenblatt-Rosen, Orit, Johnson, Bruce E., Regev, Aviv, and Wagle, Nikhil

Published
2024
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6. A multi-cohort phase 1b trial of rituximab in combination with immunotherapy doublets in relapsed/refractory follicular lymphoma

Author

Merryman, Reid W., Redd, Robert A., Freedman, Arnold S., Ahn, Inhye E., Brown, Jennifer R., Crombie, Jennifer L., Davids, Matthew S., Fisher, David C., Jacobsen, Eric D., Kim, Austin I., LaCasce, Ann S., Ng, Samuel, Odejide, Oreofe O., Parry, Erin M., Isufi, Iris, Kline, Justin, Cohen, Jonathon B., Mehta-Shah, Neha, Bartlett, Nancy L., Mei, Matthew, Kuntz, Thomas M., Wolff, Jacquelyn, Rodig, Scott J., Armand, Philippe, and Jacobson, Caron A.

Published
2024
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7. Three-Year Overall Survival Outcomes and Correlative Analyses in Patients With NSCLC and High (50%–89%) Versus Very High (≥90%) Programmed Death-Ligand 1 Expression Treated With First-Line Pembrolizumab or Cemiplimab

Author

Ricciuti, Biagio, Elkrief, Arielle, Lin, Jessica, Zhang, Jianjun, Alessi, Joao V., Lamberti, Giuseppe, Gandhi, Malini, Di Federico, Alessandro, Pecci, Federica, Wang, Xinan, Makarem, Maisam, Hidalgo Filho, Cassio Murilo, Gorria, Teresa, Saini, Arushi, Pabon, Cindy, Lindsay, James, Pfaff, Kathleen L., Welsh, Emma L., Nishino, Mizuki, Sholl, Lynette M., Rodig, Scott, Kilickap, Saadettin, Rietschel, Petra, McIntyre, Debra AG., Pouliot, Jean-Francois, Altan, Mehmet, Gainor, Justin F., Heymach, John V., Schoenfeld, Adam J., and Awad, Mark M.

Published
2024
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8. Clinical trial links oncolytic immunoactivation to survival in glioblastoma

Author

Ling, Alexander L., Solomon, Isaac H., Landivar, Ana Montalvo, Nakashima, Hiroshi, Woods, Jared K., Santos, Andres, Masud, Nafisa, Fell, Geoffrey, Mo, Xiaokui, Yilmaz, Ayse S., Grant, James, Zhang, Abigail, Bernstock, Joshua D., Torio, Erickson, Ito, Hirotaka, Liu, Junfeng, Shono, Naoyuki, Nowicki, Michal O., Triggs, Daniel, Halloran, Patrick, Piranlioglu, Raziye, Soni, Himanshu, Stopa, Brittany, Bi, Wenya Linda, Peruzzi, Pierpaolo, Chen, Ethan, Malinowski, Seth W., Prabhu, Michael C., Zeng, Yu, Carlisle, Anne, Rodig, Scott J., Wen, Patrick Y., Lee, Eudocia Quant, Nayak, Lakshmi, Chukwueke, Ugonma, Gonzalez Castro, L. Nicolas, Dumont, Sydney D., Batchelor, Tracy, Kittelberger, Kara, Tikhonova, Ekaterina, Miheecheva, Natalia, Tabakov, Dmitry, Shin, Nara, Gorbacheva, Alisa, Shumskiy, Artemy, Frenkel, Felix, Aguilar-Cordova, Estuardo, Aguilar, Laura K., Krisky, David, Wechuck, James, Manzanera, Andrea, Matheny, Chris, Tak, Paul P., Barone, Francesca, Kovarsky, Daniel, Tirosh, Itay, Suvà, Mario L., Wucherpfennig, Kai W., Ligon, Keith, Reardon, David A., and Chiocca, E. Antonio

Published
2023
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12. MITI Minimum Information guidelines for highly multiplexed tissue images

Author

Schapiro, Denis, Yapp, Clarence, Sokolov, Artem, Reynolds, Sheila M., Chen, Yu-An, Sudar, Damir, Xie, Yubin, Muhlich, Jeremy L., Arias-Camison, Raquel, Arena, Sarah, Taylor, Adam J., Nikolov, Milen, Tyler, Madison, Lin, Jia-Ren, Burlingame, Erik A., Network, Human Tumor Atlas, Chang, Young H., Farhi, Samouil L, Thorsson, Vésteinn, Venkatamohan, Nithya, Drewes, Julia L., Pe'er, Dana, Gutman, David A., Herrmann, Markus D., Gehlenborg, Nils, Bankhead, Peter, Roland, Joseph T., Herndon, John M., Snyder, Michael P., Angelo, Michael, Nolan, Garry, Swedlow, Jason R., Schultz, Nikolaus, Merrick, Daniel T., Mazzilli, Sarah A., Cerami, Ethan, Rodig, Scott J., Santagata, Sandro, and Sorger, Peter K.

Subjects
Quantitative Biology - Other Quantitative Biology, Electrical Engineering and Systems Science - Image and Video Processing
Abstract

The imminent release of tissue atlases combining multi-channel microscopy with single cell sequencing and other omics data from normal and diseased specimens creates an urgent need for data and metadata standards that guide data deposition, curation and release. We describe a Minimum Information about highly multiplexed Tissue Imaging (MITI) standard that applies best practices developed for genomics and other microscopy data to highly multiplexed tissue images and traditional histology.

Published
2021

14. Durvalumab plus tremelimumab alone or in combination with low-dose or hypofractionated radiotherapy in metastatic non-small-cell lung cancer refractory to previous PD(L)-1 therapy: an open-label, multicentre, randomised, phase 2 trial

Author

Schoenfeld, Jonathan D, Giobbie-Hurder, Anita, Ranasinghe, Srinika, Kao, Katrina Z, Lako, Ana, Tsuji, Junko, Liu, Yang, Brennick, Ryan C, Gentzler, Ryan D, Lee, Carrie, Hubbard, Joleen, Arnold, Susanne M, Abbruzzese, James L, Jabbour, Salma K, Uboha, Nataliya V, Stephans, Kevin L, Johnson, Jennifer M, Park, Haeseong, Villaruz, Liza C, Sharon, Elad, Streicher, Howard, Ahmed, Mansoor M, Lyon, Hayley, Cibuskis, Carrie, Lennon, Niall, Jhaveri, Aashna, Yang, Lin, Altreuter, Jennifer, Gunasti, Lauren, Weirather, Jason L, Mak, Raymond H, Awad, Mark M, Rodig, Scott J, Chen, Helen X, Wu, Catherine J, Monjazeb, Arta M, and Hodi, F Stephen

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Cancer, Clinical Research, Lung, Lung Cancer, Clinical Trials and Supportive Activities, 6.1 Pharmaceuticals, Evaluation of treatments and therapeutic interventions, 6.5 Radiotherapy and other non-invasive therapies, Aged, Antibodies, Monoclonal, Antibodies, Monoclonal, Humanized, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Non-Small-Cell Lung, Combined Modality Therapy, Female, Humans, Immune Checkpoint Inhibitors, Lung Neoplasms, Male, Middle Aged, Neoplasm Metastasis, Radiation Dose Hypofractionation, Radiotherapy Dosage, Oncology & Carcinogenesis, Oncology and carcinogenesis
Abstract

BackgroundPatients with non-small-cell lung cancer (NSCLC) that is resistant to PD-1 and PD-L1 (PD[L]-1)-targeted therapy have poor outcomes. Studies suggest that radiotherapy could enhance antitumour immunity. Therefore, we investigated the potential benefit of PD-L1 (durvalumab) and CTLA-4 (tremelimumab) inhibition alone or combined with radiotherapy.MethodsThis open-label, multicentre, randomised, phase 2 trial was done by the National Cancer Institute Experimental Therapeutics Clinical Trials Network at 18 US sites. Patients aged 18 years or older with metastatic NSCLC, an Eastern Cooperative Oncology Group performance status of 0 or 1, and progression during previous PD(L)-1 therapy were eligible. They were randomly assigned (1:1:1) in a web-based system by the study statistician using a permuted block scheme (block sizes of three or six) without stratification to receive either durvalumab (1500 mg intravenously every 4 weeks for a maximum of 13 cycles) plus tremelimumab (75 mg intravenously every 4 weeks for a maximum of four cycles) alone or with low-dose (0·5 Gy delivered twice per day, repeated for 2 days during each of the first four cycles of therapy) or hypofractionated radiotherapy (24 Gy total delivered over three 8-Gy fractions during the first cycle only), 1 week after initial durvalumab-tremelimumab administration. Study treatment was continued until 1 year or until progression. The primary endpoint was overall response rate (best locally assessed confirmed response of a partial or complete response) and, along with safety, was analysed in patients who received at least one dose of study therapy. The trial is registered with ClinicalTrials.gov, NCT02888743, and is now complete.FindingsBetween Aug 24, 2017, and March 29, 2019, 90 patients were enrolled and randomly assigned, of whom 78 (26 per group) were treated. This trial was stopped due to futility assessed in an interim analysis. At a median follow-up of 12·4 months (IQR 7·8-15·1), there were no differences in overall response rates between the durvalumab-tremelimumab alone group (three [11·5%, 90% CI 1·2-21·8] of 26 patients) and the low-dose radiotherapy group (two [7·7%, 0·0-16·3] of 26 patients; p=0·64) or the hypofractionated radiotherapy group (three [11·5%, 1·2-21·8] of 26 patients; p=0·99). The most common grade 3-4 adverse events were dyspnoea (two [8%] in the durvalumab-tremelimumab alone group; three [12%] in the low-dose radiotherapy group; and three [12%] in the hypofractionated radiotherapy group) and hyponatraemia (one [4%] in the durvalumab-tremelimumab alone group vs two [8%] in the low-dose radiotherapy group vs three [12%] in the hypofractionated radiotherapy group). Treatment-related serious adverse events occurred in one (4%) patient in the durvalumab-tremelimumab alone group (maculopapular rash), five (19%) patients in the low-dose radiotherapy group (abdominal pain, diarrhoea, dyspnoea, hypokalemia, and respiratory failure), and four (15%) patients in the hypofractionated group (adrenal insufficiency, colitis, diarrhoea, and hyponatremia). In the low-dose radiotherapy group, there was one death from respiratory failure potentially related to study therapy.InterpretationRadiotherapy did not increase responses to combined PD-L1 plus CTLA-4 inhibition in patients with NSCLC resistant to PD(L)-1 therapy. However, PD-L1 plus CTLA-4 therapy could be a treatment option for some patients. Future studies should refine predictive biomarkers in this setting.FundingThe US National Institutes of Health and the Dana-Farber Cancer Institute.

Published
2022

15. Comprehensive Immunoprofiling of High-Risk Oral Proliferative and Localized LeukoplakiaImmunoprofiling High-Risk Oral Leukoplakia

Author

Hanna, Glenn J, Villa, Alessandro, Mistry, Nikhil, Jia, Yonghui, Quinn, Charles T, Turner, Madison M, Felt, Kristen D, Pfaff, Kathleen, Haddad, Robert I, Uppaluri, Ravindra, Rodig, Scott J, Woo, Sook-Bin, Egloff, Ann Marie, and Hodi, F Stephen

Subjects
Biomedical and Clinical Sciences, Oncology and Carcinogenesis, Immunology, Digestive Diseases, Rare Diseases, Prevention, Cancer, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, Humans, CD8-Positive T-Lymphocytes, B7-H1 Antigen, Programmed Cell Death 1 Receptor, Leukoplakia, Oral, Gene Expression Profiling, Tumor Microenvironment
Abstract

Oral leukoplakia is common and may, in some cases, progress to carcinoma. Proliferative leukoplakia is a progressive, often multifocal subtype with a high rate of malignant transformation compared with the more common localized leukoplakia. We hypothesized that the immune microenvironment and gene expression patterns would be distinct for proliferative leukoplakia compared with localized leukoplakia. We summarize key clinicopathologic features among proliferative leukoplakia and localized leukoplakia and compare cancer-free survival (CFS) between subgroups. We analyze immunologic gene expression profiling in proliferative leukoplakia and localized leukoplakia tissue samples (NanoString PanCancer Immune Oncology Profiling). We integrate immune cell activation and spatial distribution patterns in tissue samples using multiplexed immunofluorescence and digital image capture to further define proliferative leukoplakia and localized leukoplakia. Among N = 58 patients (proliferative leukoplakia, n = 29; localized leukoplakia, n = 29), only the clinical diagnosis of proliferative leukoplakia was associated with significantly decreased CFS (HR, 11.25; P < 0.01; 5-year CFS 46.8% and 83.6% among patients with proliferative leukoplakia and localized leukoplakia, respectively). CD8+ T cells and T regulatory (Treg) were more abundant among proliferative leukoplakia samples (P < 0.01) regardless of degree of epithelial dysplasia, and often colocalized to the dysplasia-stromal interface. Gene set analysis identified granzyme M as the most differentially expressed gene favoring the proliferative leukoplakia subgroup (log2 fold change, 1.93; P adj < 0.001). Programmed death ligand 1 (PD-L1) was comparatively overexpressed among proliferative leukoplakia samples, with higher (>5) PD-L1 scores predicting worse CFS (P adj < 0.01). Proliferative leukoplakia predicts a high rate of malignant transformation within 5 years of diagnosis. A prominent CD8+ T-cell and Treg signature along with relative PD-L1 overexpression compared with localized leukoplakia provides strong rationale for PD-1/PD-L1 axis blockade using preventative immunotherapy.SignificanceThis is the first in-depth profiling effort to immunologically characterize high-risk proliferative leukoplakia as compared with the more common localized leukoplakia. We observed a notable cytotoxic T-cell and Treg signature with relative overexpression of PD-L1 in high-risk proliferative leukoplakia providing a strong preclinical rationale for investigating PD-1/PD-L1 axis blockade in this disease as preventative immunotherapy.

Published
2021

16. Multiplex Tissue Imaging Harmonization: A Multicenter Experience from CIMAC-CIDC Immuno-Oncology Biomarkers Network

Author

Akturk, Guray, Parra, Edwin R, Gjini, Evisa, Lako, Ana, Lee, J Jack, Neuberg, Donna, Zhang, Jiexin, Yao, Shen, Laface, Ilaria, Rogic, Anita, Chen, Pei-Hsuan, Sanchez-Espiridion, Beatriz, Del Valle, Diane M, Moravec, Radim, Kinders, Robert, Hudgens, Courtney, Wu, Catherine, Wistuba, Ignacio I, Thurin, Magdalena, Hewitt, Stephen M, Rodig, Scott, Gnjatic, Sacha, and Tetzlaff, Michael T

Subjects
Biotechnology, Clinical Research, Vaccine Related, Clinical Trials and Supportive Activities, Cancer, Biomarkers, Tumor, Fluorescent Antibody Technique, Humans, Image Processing, Computer-Assisted, Monitoring, Immunologic, Neoplasms, Staining and Labeling, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeThe Cancer Immune Monitoring and Analysis Centers - Cancer Immunologic Data Commons (CIMAC-CIDC) network supported by the NCI Cancer Moonshot initiative was established to provide correlative analyses for clinical trials in cancer immunotherapy, using state-of-the-art technology. Fundamental to this initiative is implementation of multiplex IHC assays to define the composition and distribution of immune infiltrates within tumors in the context of their potential role as biomarkers. A critical unanswered question involves the relative fidelity of such assays to reliably quantify tumor-associated immune cells across different platforms.Experimental designThree CIMAC sites compared across their laboratories: (i) image analysis algorithms, (ii) image acquisition platforms, (iii) multiplex staining protocols. Two distinct high-dimensional approaches were employed: multiplexed IHC consecutive staining on single slide (MICSSS) and multiplexed immunofluorescence (mIF). To eliminate variables potentially impacting assay performance, we completed a multistep harmonization process, first comparing assay performance using independent protocols followed by the integration of laboratory-specific protocols and finally, validating this harmonized approach in an independent set of tissues.ResultsData generated at the final validation step showed an intersite Spearman correlation coefficient (r) of ≥0.85 for each marker within and across tissue types, with an overall low average coefficient of variation ≤0.1.ConclusionsOur results support interchangeability of protocols and platforms to deliver robust, and comparable data using similar tissue specimens and confirm that CIMAC-CIDC analyses may therefore be used with confidence for statistical associations with clinical outcomes largely independent of site, antibody selection, protocol, and platform across different sites.

Published
2021

17. Cutaneous Manifestations of Myeloid Neoplasms Exhibit Broad and Divergent Morphologic and Immunophenotypic Features but Share Ancestral Clonal Mutations With Bone Marrow

Author

Sadigh, Sam, DeAngelo, Daniel J., Garcia, Jacqueline S., Hasserjian, Robert P., Hergott, Christopher B., Lane, Andrew A., Lovitch, Scott B., Lucas, Fabienne, Luskin, Marlise R., Morgan, Elizabeth A., Pinkus, Geraldine S., Pozdnyakova, Olga, Rodig, Scott J., Shanmugam, Vignesh, Tsai, Harrison K., Winer, Eric S., Zemmour, David, and Kim, Annette S.

Published
2024
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18. Pathomic Fusion: An Integrated Framework for Fusing Histopathology and Genomic Features for Cancer Diagnosis and Prognosis

Author

Chen, Richard J., Lu, Ming Y., Wang, Jingwen, Williamson, Drew F. K., Rodig, Scott J., Lindeman, Neal I., and Mahmood, Faisal

Subjects
Computer Science - Computer Vision and Pattern Recognition, Quantitative Biology - Genomics, Quantitative Biology - Tissues and Organs
Abstract

Cancer diagnosis, prognosis, and therapeutic response predictions are based on morphological information from histology slides and molecular profiles from genomic data. However, most deep learning-based objective outcome prediction and grading paradigms are based on histology or genomics alone and do not make use of the complementary information in an intuitive manner. In this work, we propose Pathomic Fusion, an interpretable strategy for end-to-end multimodal fusion of histology image and genomic (mutations, CNV, RNA-Seq) features for survival outcome prediction. Our approach models pairwise feature interactions across modalities by taking the Kronecker product of unimodal feature representations and controls the expressiveness of each representation via a gating-based attention mechanism. Following supervised learning, we are able to interpret and saliently localize features across each modality, and understand how feature importance shifts when conditioning on multimodal input. We validate our approach using glioma and clear cell renal cell carcinoma datasets from the Cancer Genome Atlas (TCGA), which contains paired whole-slide image, genotype, and transcriptome data with ground truth survival and histologic grade labels. In a 15-fold cross-validation, our results demonstrate that the proposed multimodal fusion paradigm improves prognostic determinations from ground truth grading and molecular subtyping, as well as unimodal deep networks trained on histology and genomic data alone. The proposed method establishes insight and theory on how to train deep networks on multimodal biomedical data in an intuitive manner, which will be useful for other problems in medicine that seek to combine heterogeneous data streams for understanding diseases and predicting response and resistance to treatment., Comment: Code and trained models are made available at: https://github.com/mahmoodlab/PathomicFusion

Published
2019

19. A Randomized Trial of Combined PD-L1 and CTLA-4 Inhibition with Targeted Low-Dose or Hypofractionated Radiation for Patients with Metastatic Colorectal CancerPD-L1/CTLA-4 Inhibition with Radiation for Colorectal Cancer

Author

Monjazeb, Arta M, Giobbie-Hurder, Anita, Lako, Ana, Thrash, Emily M, Brennick, Ryan C, Kao, Katrina Z, Manuszak, Claire, Gentzler, Ryan D, Tesfaye, Anteneh, Jabbour, Salma K, Alese, Olatunji B, Rahma, Osama E, Cleary, James M, Sharon, Elad, Mamon, Harvey J, Cho, May, Streicher, Howard, Chen, Helen X, Ahmed, Mansoor M, Mariño-Enríquez, Adrian, Kim-Schulze, Seunghee, Gnjatic, Sacha, Maverakis, Emanual, Marusina, Alina I, Merleev, Alexander A, Severgnini, Mariano, Pfaff, Kathleen L, Lindsay, James, Weirather, Jason L, Ranasinghe, Srinika, Spektor, Alexander, Rodig, Scott J, Hodi, F Stephen, and Schoenfeld, Jonathan D

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Immunology, Cancer, Radiation Oncology, Clinical Trials and Supportive Activities, Colo-Rectal Cancer, Clinical Research, Immunotherapy, Digestive Diseases, Evaluation of treatments and therapeutic interventions, 6.1 Pharmaceuticals, Antineoplastic Combined Chemotherapy Protocols, B7-H1 Antigen, Biomarkers, CTLA-4 Antigen, Colorectal Neoplasms, Combined Modality Therapy, Gene Expression Profiling, Humans, Immune Checkpoint Inhibitors, Molecular Targeted Therapy, Neoplasm Metastasis, Neoplasm Staging, Radiation Dose Hypofractionation, Treatment Outcome, Oncology & Carcinogenesis, Clinical sciences, Oncology and carcinogenesis
Abstract

PurposeProspective human data are lacking regarding safety, efficacy, and immunologic impacts of different radiation doses administered with combined PD-L1/CTLA-4 blockade.Patients and methodsWe performed a multicenter phase II study randomly assigning patients with metastatic microsatellite stable colorectal cancer to repeated low-dose fractionated radiation (LDFRT) or hypofractionated radiation (HFRT) with PD-L1/CTLA-4 inhibition. The primary endpoint was response outside the radiation field. Correlative samples were analyzed using multiplex immunofluorescence (IF), IHC, RNA/T-cell receptor (TCR) sequencing, cytometry by time-of-flight (CyTOF), and Olink.ResultsEighteen patients were evaluable for response. Median lines of prior therapy were four (range, 1-7). Sixteen patients demonstrated toxicity potentially related to treatment (84%), and 8 patients had grade 3-4 toxicity (42%). Best response was stable disease in 1 patient with out-of-field tumor shrinkage. Median overall survival was 3.8 months (90% confidence interval, 2.3-5.7 months). Correlative IF and RNA sequencing (RNA-seq) revealed increased infiltration of CD8+ and CD8+/PD-1+/Ki-67+ T cells in the radiation field after HFRT. LDFRT increased foci of micronuclei/primary nuclear rupture in two subjects. CyTOF and RNA-seq demonstrated significant declines in multiple circulating immune populations, particularly in patients receiving HFRT. TCR sequencing revealed treatment-associated changes in T-cell repertoire in the tumor and peripheral blood.ConclusionsWe demonstrate the feasibility and safety of adding LDFRT and HFRT to PD-L1/CTLA-4 blockade. Although the best response of stable disease does not support the use of concurrent PD-L1/CTLA-4 inhibition with HFRT or LDFRT in this population, biomarkers provide support that both LDFRT and HFRT impact the local immune microenvironment and systemic immunogenicity that can help guide future studies.

Published
2021

20. Association of Baseline Tumor-Specific Neoantigens and CD8+ T-Cell Infiltration With Immune-Related Adverse Events Secondary to Immune Checkpoint Inhibitors

Author

Kerepesi, Csaba, Abushukair, Hassan Mohammed, Ricciuti, Biagio, Nassar, Amin H., Adib, Elio, Alessi, Joao V., Pecci, Federica, Rakaee, Mehrdad, Fadlullah, Muhammad Zaki Hidayatullah, Tőkés, Anna-Mária, Rodig, Scott J., Awad, Mark M., Tan, Aik Choon, Bakacs, Tibor, and Naqash, Abdul Rafeh

Published
2024
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21. Impact of Aneuploidy and Chromosome 9p Loss on Tumor Immune Microenvironment and Immune Checkpoint Inhibitor Efficacy in NSCLC

Author

Alessi, Joao V., Wang, Xinan, Elkrief, Arielle, Ricciuti, Biagio, Li, Yvonne Y., Gupta, Hersh, Spurr, Liam F., Rizvi, Hira, Luo, Jia, Pecci, Federica, Lamberti, Giuseppe, Recondo, Gonzalo, Venkatraman, Deepti, Di Federico, Alessandro, Gandhi, Malini M., Vaz, Victor R., Nishino, Mizuki, Sholl, Lynette M., Cherniack, Andrew D., Ladanyi, Marc, Price, Adam, Richards, Allison L., Donoghue, Mark, Lindsay, James, Sharma, Bijaya, Turner, Madison M., Pfaff, Kathleen L., Felt, Kristen D., Rodig, Scott J., Lin, Xihong, Meyerson, Matthew L., Johnson, Bruce E., Christiani, David C., Schoenfeld, Adam J., and Awad, Mark M.

Published
2023
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25. Neoadjuvant and Adjuvant Pembrolizumab in Resectable Locally Advanced, Human Papillomavirus–Unrelated Head and Neck Cancer: A Multicenter, Phase II Trial

Author

Uppaluri, Ravindra, Campbell, Katie M, Egloff, Ann Marie, Zolkind, Paul, Skidmore, Zachary L, Nussenbaum, Brian, Paniello, Randal C, Rich, Jason T, Jackson, Ryan, Pipkorn, Patrik, Michel, Loren S, Ley, Jessica, Oppelt, Peter, Dunn, Gavin P, Barnell, Erica K, Spies, Nicholas C, Lin, Tianxiang, Li, Tiantian, Mulder, David T, Hanna, Youstina, Cirlan, Iulia, Pugh, Trevor J, Mudianto, Tenny, Riley, Rachel, Zhou, Liye, Jo, Vickie Y, Stachler, Matthew D, Hanna, Glenn J, Kass, Jason, Haddad, Robert, Schoenfeld, Jonathan D, Gjini, Evisa, Lako, Ana, Thorstad, Wade, Gay, Hiram A, Daly, Mackenzie, Rodig, Scott J, Hagemann, Ian S, Kallogjeri, Dorina, Piccirillo, Jay F, Chernock, Rebecca D, Griffith, Malachi, Griffith, Obi L, and Adkins, Douglas R

Subjects
Clinical Research, Sexually Transmitted Infections, Patient Safety, Infectious Diseases, Cancer, Dental/Oral and Craniofacial Disease, Rare Diseases, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, B7-H1 Antigen, Chemotherapy, Adjuvant, Drug-Related Side Effects and Adverse Reactions, Female, Humans, Interferon-gamma, Lymphocytes, Tumor-Infiltrating, Male, Middle Aged, Neoadjuvant Therapy, Neoplasm Recurrence, Local, Papillomaviridae, Squamous Cell Carcinoma of Head and Neck, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposePembrolizumab improved survival in patients with recurrent or metastatic head and neck squamous-cell carcinoma (HNSCC). The aims of this study were to determine if pembrolizumab would be safe, result in pathologic tumor response (pTR), and lower the relapse rate in patients with resectable human papillomavirus (HPV)-unrelated HNSCC.Patients and methodsNeoadjuvant pembrolizumab (200 mg) was administered and followed 2 to 3 weeks later by surgical tumor ablation. Postoperative (chemo)radiation was planned. Patients with high-risk pathology (positive margins and/or extranodal extension) received adjuvant pembrolizumab. pTR was quantified as the proportion of the resection bed with tumor necrosis, keratinous debris, and giant cells/histiocytes: pTR-0 (

Published
2020

26. Mechanisms of response and resistance to combined decitabine and ipilimumab for advanced myeloid disease

Author

Penter, Livius, Liu, Yang, Wolff, Jacquelyn O., Yang, Lin, Taing, Len, Jhaveri, Aashna, Southard, Jackson, Patel, Manishkumar, Cullen, Nicole M., Pfaff, Kathleen L., Cieri, Nicoletta, Oliveira, Giacomo, Kim-Schulze, Seunghee, Ranasinghe, Srinika, Leonard, Rebecca, Robertson, Taylor, Morgan, Elizabeth A., Chen, Helen X., Song, Minkyung H., Thurin, Magdalena, Li, Shuqiang, Rodig, Scott J., Cibulskis, Carrie, Gabriel, Stacey, Bachireddy, Pavan, Ritz, Jerome, Streicher, Howard, Neuberg, Donna S., Hodi, F. Stephen, Davids, Matthew S., Gnjatic, Sacha, Livak, Kenneth J., Altreuter, Jennifer, Michor, Franziska, Soiffer, Robert J., Garcia, Jacqueline S., and Wu, Catherine J.

Published
2023
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27. Proceedings of the fifth international Molecular Pathological Epidemiology (MPE) meeting

Author

Yao, Song, Campbell, Peter T., Ugai, Tomotaka, Gierach, Gretchen, Abubakar, Mustapha, Adalsteinsson, Viktor, Almeida, Jonas, Brennan, Paul, Chanock, Stephen, Golub, Todd, Hanash, Samir, Harris, Curtis, Hathaway, Cassandra A., Kelsey, Karl, Landi, Maria Teresa, Mahmood, Faisal, Newton, Christina, Quackenbush, John, Rodig, Scott, Schultz, Nikolaus, Tearney, Guillermo, Tworoger, Shelley S., Wang, Molin, Zhang, Xuehong, Garcia-Closas, Montserrat, Rebbeck, Timothy R., Ambrosone, Christine B., and Ogino, Shuji

Published
2022
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29. The identification of TCF1+ progenitor exhausted T cells in THRLBCL may predict a better response to PD-1/PD-L1 blockade

Author

Tabanelli, Valentina, Melle, Federica, Motta, Giovanna, Mazzara, Saveria, Fabbri, Marco, Agostinelli, Claudio, Calleri, Angelica, Del Corvo, Marcello, Fiori, Stefano, Lorenzini, Daniele, Cesano, Alessandra, Chiappella, Annalisa, Vitolo, Umberto, Derenzini, Enrico, Griffin, Gabriel K., Rodig, Scott J., Vanazzi, Anna, Sabattini, Elena, Tarella, Corrado, Sapienza, Maria Rosaria, and Pileri, Stefano A.

Published
2022
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30. Landscape of helper and regulatory antitumour CD4+ T cells in melanoma

Author

Oliveira, Giacomo, Stromhaug, Kari, Cieri, Nicoletta, Iorgulescu, J. Bryan, Klaeger, Susan, Wolff, Jacquelyn O., Rachimi, Suzanna, Chea, Vipheaviny, Krause, Kate, Freeman, Samuel S., Zhang, Wandi, Li, Shuqiang, Braun, David A., Neuberg, Donna, Carr, Steven A., Livak, Kenneth J., Frederick, Dennie T., Fritsch, Edward F., Wind-Rotolo, Megan, Hacohen, Nir, Sade-Feldman, Moshe, Yoon, Charles H., Keskin, Derin B., Ott, Patrick A., Rodig, Scott J., Boland, Genevieve M., and Wu, Catherine J.

Published
2022
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31. MITI minimum information guidelines for highly multiplexed tissue images

Author

Schapiro, Denis, Yapp, Clarence, Sokolov, Artem, Reynolds, Sheila M., Chen, Yu-An, Sudar, Damir, Xie, Yubin, Muhlich, Jeremy, Arias-Camison, Raquel, Arena, Sarah, Taylor, Adam J., Nikolov, Milen, Tyler, Madison, Lin, Jia-Ren, Burlingame, Erik A., Chang, Young H., Farhi, Samouil L., Thorsson, Vésteinn, Venkatamohan, Nithya, Drewes, Julia L., Pe’er, Dana, Gutman, David A., Herrmann, Markus D., Gehlenborg, Nils, Bankhead, Peter, Roland, Joseph T., Herndon, John M., Snyder, Michael P., Angelo, Michael, Nolan, Garry, Swedlow, Jason R., Schultz, Nikolaus, Merrick, Daniel T., Mazzili, Sarah A., Cerami, Ethan, Rodig, Scott J., Santagata, Sandro, and Sorger, Peter K.

Published
2022
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32. A randomized phase 2 study of neoadjuvant carboplatin and paclitaxel with or without atezolizumab in triple negative breast cancer (TNBC) - NCI 10013

Author

Ademuyiwa, Foluso O., Gao, Feng, Street, Cherease R., Chen, Ina, Northfelt, Donald W., Wesolowski, Robert, Arora, Mili, Brufsky, Adam, Dees, E. Claire, Santa-Maria, Cesar A., Connolly, Roisin M., Force, Jeremy, Moreno-Aspitia, Alvaro, Herndon, John M., Carmody, Madelyn, Davies, Sherri R., Larson, Sarah, Pfaff, Kathleen L., Jones, Stephanie M., Weirather, Jason L., Giobbie-Hurder, Anita, Rodig, Scott J., Liu, Zheng, Hagemann, Ian S., Sharon, Elad, and Gillanders, William E.

Published
2022
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33. Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses

Author

Cañadas, Israel, Thummalapalli, Rohit, Kim, Jong Wook, Kitajima, Shunsuke, Jenkins, Russell William, Christensen, Camilla Laulund, Campisi, Marco, Kuang, Yanan, Zhang, Yanxi, Gjini, Evisa, Zhang, Gao, Tian, Tian, Sen, Debattama Rai, Miao, Diana, Imamura, Yu, Thai, Tran, Piel, Brandon, Terai, Hideki, Aref, Amir Reza, Hagan, Timothy, Koyama, Shohei, Watanabe, Masayuki, Baba, Hideo, Adeni, Anika Elise, Lydon, Christine Anne, Tamayo, Pablo, Wei, Zhi, Herlyn, Meenhard, Barbie, Thanh Uyen, Uppaluri, Ravindra, Sholl, Lynnette Marie, Sicinska, Ewa, Sands, Jacob, Rodig, Scott, Wong, Kwok Kin, Paweletz, Cloud Peter, Watanabe, Hideo, and Barbie, David Allen

Subjects
Genetics, Cancer, Vaccine Related, Immunization, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Animals, Cell Line, Tumor, Endogenous Retroviruses, Gene Expression Regulation, Neoplastic, Humans, Immunity, Innate, Interferons, Mice, Nude, Neoplasms, RNA, Antisense, Medical and Health Sciences, Immunology
Abstract

Mesenchymal tumor subpopulations secrete pro-tumorigenic cytokines and promote treatment resistance1-4. This phenomenon has been implicated in chemorefractory small cell lung cancer and resistance to targeted therapies5-8, but remains incompletely defined. Here, we identify a subclass of endogenous retroviruses (ERVs) that engages innate immune signaling in these cells. Stimulated 3 prime antisense retroviral coding sequences (SPARCS) are oriented inversely in 3' untranslated regions of specific genes enriched for regulation by STAT1 and EZH2. Derepression of these loci results in double-stranded RNA generation following IFN-γ exposure due to bi-directional transcription from the STAT1-activated gene promoter and the 5' long terminal repeat of the antisense ERV. Engagement of MAVS and STING activates downstream TBK1, IRF3, and STAT1 signaling, sustaining a positive feedback loop. SPARCS induction in human tumors is tightly associated with major histocompatibility complex class 1 expression, mesenchymal markers, and downregulation of chromatin modifying enzymes, including EZH2. Analysis of cell lines with high inducible SPARCS expression reveals strong association with an AXL/MET-positive mesenchymal cell state. While SPARCS-high tumors are immune infiltrated, they also exhibit multiple features of an immune-suppressed microenviroment. Together, these data unveil a subclass of ERVs whose derepression triggers pathologic innate immune signaling in cancer, with important implications for cancer immunotherapy.

Published
2018

34. Cross-domain information fusion for enhanced cell population delineation in single-cell spatial-omics data

Author

Zhu, Bokai, primary, Gao, Sheng, additional, Chen, Shuxiao, additional, Yeung, Jason, additional, Bai, Yunhao, additional, Huang, Amy, additional, Yeo, Yao Yu, additional, Liao, Guanrui, additional, Mao, Shulian, additional, Jiang, Zhenghui, additional, Rodig, Scott, additional, Shalek, Alex K, additional, Nolan, Garry P, additional, Jiang, Sizun, additional, and Ma, Zongming, additional

Published
2024
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35. Three-year overall survival outcomes and correlative analyses in patients with non–small-cell lung cancer and high (50-89%) versus very high (≥90%) PD-L1 expression treated with first-line pembrolizumab or cemiplimab

Author

Ricciuti, Biagio, primary, Elkrief, Arielle, additional, Lin, Jessica, additional, Zhang, Jianjun, additional, Alessi, Joao V., additional, Lamberti, Giuseppe, additional, Gandhi, Malini, additional, Di Federico, Alessandro, additional, Pecci, Federica, additional, Wang, Xinan, additional, Makarem, Maisam, additional, Hidalgo Filho, Cassio Murilo, additional, Gorria, Teresa, additional, Pabon, Cindy, additional, Lindsay, James, additional, Pfaff, Kathleen L., additional, Welsh, Emma L., additional, Nishino, Mizuki, additional, Sholl, Lynette M., additional, Rodig, Scott, additional, Kilickap, Saadettin, additional, Rietschel, Petra, additional, McIntyre, Debra AG., additional, Pouliot, Jean-Francois, additional, Altan, Mehmet, additional, Gainor, Justin F., additional, Heymach, John V., additional, Schoenfeld, Adam J., additional, and Awad, Mark M., additional

Published
2024
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36. Epstein-Barr Virus Orchestrates Spatial Reorganization and Immunomodulation within the Classic Hodgkin Lymphoma Tumor Microenvironment

Author

Yeo, Yao Yu, primary, Qiu, Huaying, additional, Bai, Yunhao, additional, Zhu, Bokai, additional, Chang, Yuzhou, additional, Yeung, Jason, additional, Michel, Hendrik A., additional, Wright, Kyle, additional, Shaban, Muhammad, additional, Sadigh, Sam, additional, Nkosi, Dingani, additional, Shanmugam, Vignesh, additional, Rock, Philip, additional, Tung Yiu, Stephanie Pei, additional, Cramer, Precious, additional, Paczkowska, Julia, additional, Stephan, Pierre, additional, Liao, Guanrui, additional, Huang, Amy Y., additional, Wang, Hongbo, additional, Chen, Han, additional, Frauenfeld, Leonie, additional, Mitra, Bidisha, additional, Gewurz, Benjamin E., additional, Schürch, Christian M., additional, Zhao, Bo, additional, Nolan, Garry P., additional, Zhang, Baochun, additional, Shalek, Alex K., additional, Angelo, Michael, additional, Mahmood, Faisal, additional, Ma, Qin, additional, Burack, W. Richard, additional, Shipp, Margaret A., additional, Rodig, Scott J., additional, and Jiang, Sizun, additional

Published
2024
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40. Spatial signatures identify immune escape via PD-1 as a defining feature of T-cell/histiocyte-rich large B-cell lymphoma

Author

Griffin, Gabriel K., Weirather, Jason L., Roemer, Margaretha G.M., Lipschitz, Mikel, Kelley, Alyssa, Chen, Pei-Hsuan, Gusenleitner, Daniel, Jeter, Erin, Pak, Christine, Gjini, Evisa, Chapuy, Bjoern, Rosenthal, Michael H., Xu, Jie, Chen, Benjamin J., Sohani, Aliyah R., Lovitch, Scott B., Abramson, Jeremy S., Ishizuka, Jeffrey J., Kim, Austin I., Jacobson, Caron A., LaCasce, Ann S., Fletcher, Christopher D., Neuberg, Donna, Freeman, Gordon J., Hodi, F. Stephen, Wright, Kyle, Ligon, Azra H., Jacobsen, Eric D., Armand, Philippe, Shipp, Margaret A., and Rodig, Scott J.

Published
2021
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41. Association of Baseline Tumor-Specific Neoantigens and CD8 + T-Cell Infiltration With Immune-Related Adverse Events Secondary to Immune Checkpoint Inhibitors.

Author

Kerepesi, Csaba, Abushukair, Hassan Mohammed, Ricciuti, Biagio, Nassar, Amin H., Adib, Elio, Alessi, Joao V., Pecci, Federica, Rakaee, Mehrdad, Fadlullah, Muhammad Zaki Hidayatullah, Tőkés, Anna-Mária, Rodig, Scott J., Awad, Mark M., Tan, Aik Choon, Bakacs, Tibor, and Naqash, Abdul Rafeh

Abstract

PURPOSE: Recent evidence has shown that higher tumor mutational burden strongly correlates with an increased risk of immune-related adverse events (irAEs). By using an integrated multiomics approach, we further studied the association between relevant tumor immune microenvironment (TIME) features and irAEs. METHODS: Leveraging the US Food and Drug Administration Adverse Event Reporting System, we extracted cases of suspected irAEs to calculate the reporting odds ratios (RORs) of irAEs for cancers treated with immune checkpoint inhibitors (ICIs). TIME features for 32 cancer types were calculated on the basis of the cancer genomic atlas cohorts and indirectly correlated with each cancer's ROR for irAEs. A separate ICI-treated cohort of non–small-cell lung cancer (NSCLC) was used to evaluate the correlation between tissue-based immune markers (CD8+, PD-1/L1+, FOXP3+, tumor-infiltrating lymphocytes [TILs]) and irAE occurrence. RESULTS: The analysis of 32 cancers and 33 TIME features demonstrated a significant association between irAE RORs and the median number of base insertions and deletions (INDEL), neoantigens (r = 0.72), single-nucleotide variant neoantigens (r = 0.67), and CD8+ T-cell fraction (r = 0.51). A bivariate model using the median number of INDEL neoantigens and CD8 T-cell fraction had the highest accuracy in predicting RORs (adjusted r2 = 0.52, P =.002). Immunoprofile assessment of 156 patients with NSCLC revealed a strong trend for higher baseline median CD8+ T cells within patients' tumors who experienced any grade irAEs. Using machine learning, an expanded ICI-treated NSCLC cohort (n = 378) further showed a treatment duration–independent association of an increased proportion of high TIL (>median) in patients with irAEs (59.7% v 44%, P =.005). This was confirmed by using the Fine-Gray competing risk approach, demonstrating higher baseline TIL density (>median) associated with a higher cumulative incidence of irAEs (P =.028). CONCLUSION: Our findings highlight a potential role for TIME features, specifically INDEL neoantigens and baseline-immune infiltration, in enabling optimal irAE risk stratification of patients. [ABSTRACT FROM AUTHOR]

Published
2024
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43. Personal neoantigen vaccines induce persistent memory T cell responses and epitope spreading in patients with melanoma

Author

Hu, Zhuting, Leet, Donna E., Allesøe, Rosa L., Oliveira, Giacomo, Li, Shuqiang, Luoma, Adrienne M., Liu, Jinyan, Forman, Juliet, Huang, Teddy, Iorgulescu, J. Bryan, Holden, Rebecca, Sarkizova, Siranush, Gohil, Satyen H., Redd, Robert A., Sun, Jing, Elagina, Liudmila, Giobbie-Hurder, Anita, Zhang, Wandi, Peter, Lauren, Ciantra, Zoe, Rodig, Scott, Olive, Oriol, Shetty, Keerthi, Pyrdol, Jason, Uduman, Mohamed, Lee, Patrick C., Bachireddy, Pavan, Buchbinder, Elizabeth I., Yoon, Charles H., Neuberg, Donna, Pentelute, Bradley L., Hacohen, Nir, Livak, Kenneth J., Shukla, Sachet A., Olsen, Lars Rønn, Barouch, Dan H., Wucherpfennig, Kai W., Fritsch, Edward F., Keskin, Derin B., Wu, Catherine J., and Ott, Patrick A.

Published
2021
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45. PD-1 blockade for diffuse large B-cell lymphoma after autologous stem cell transplantation

Author

Frigault, Matthew J., Armand, Philippe, Redd, Robert A., Jeter, Erin, Merryman, Reid W., Coleman, Kimberly C., Herrera, Alex F., Dahi, Parastoo, Nieto, Yago, LaCasce, Ann S., Fisher, David C., Ng, Samuel Y., Odejide, Oreife O., Freedman, Arnold S., Kim, Austin I., Crombie, Jennifer L., Jacobson, Caron A., Jacobsen, Eric D., Wong, Jeffrey L., Bsat, Jad, Patel, Sanjay S., Ritz, Jerome, Rodig, Scott J., Shipp, Margaret A., Chen, Yi-Bin, and Joyce, Robin M.

Published
2020
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46. Multidimensional Molecular Profiling of Metastatic Triple-Negative Breast Cancer and Immune Checkpoint Inhibitor Benefit

Author

Barroso-Sousa, Romualdo, Forman, Juliet, Collier, Katharine, Weber, Zachary T., Jammihal, Tejas R., Kao, Katrina Z., Richardson, Edward T., III, Keenan, Tanya, Cohen, Ofir, Manos, Michael P., Brennick, Ryan C., Ott, Patrick A., Hodi, F. Stephen, Dillon, Deborah A., Attaya, Victoria, OʼMeara, Tess, Lin, Nancy U., Van Allen, Eliezer M., Rodig, Scott, Winer, Eric P., Mittendorf, Elizabeth A., Wu, Catherine J., Wagle, Nikhil, Stover, Daniel G., Shukla, Sachet A., and Tolaney, Sara M.

Published
2022
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47. Graph Fourier transform for spatial omics representation and analyses of complex organs

Author

Ma, Qin, primary, Chang, Yuzhou, additional, Liu, Jixin, additional, Jiang, Yi, additional, Ma, Anjun, additional, Yeo, Yao Yu, additional, Guo, Qi, additional, McNutt, Megan, additional, Krull, Jodran, additional, Rodig, Scott, additional, Barouch, Dan, additional, Nolan, Garry, additional, Xu, Dong, additional, Jiang, Sizun, additional, Li, Zihai, additional, and Liu, Bingqiang, additional

Published
2024
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48. A spatial cell atlas of neuroblastoma reveals developmental, epigenetic and spatial axis of tumor heterogeneity

Author

Patel, Anand G., primary, Ashenberg, Orr, additional, Collins, Natalie B., additional, Segerstolpe, Åsa, additional, Jiang, Sizun, additional, Slyper, Michal, additional, Huang, Xin, additional, Caraccio, Chiara, additional, Jin, Hongjian, additional, Sheppard, Heather, additional, Xu, Ke, additional, Chang, Ti-Cheng, additional, Orr, Brent A., additional, Shirinifard, Abbas, additional, Chapple, Richard H., additional, Shen, Amber, additional, Clay, Michael R., additional, Tatevossian, Ruth G., additional, Reilly, Colleen, additional, Patel, Jaimin, additional, Lupo, Marybeth, additional, Cline, Cynthia, additional, Dionne, Danielle, additional, Porter, Caroline B.M., additional, Waldman, Julia, additional, Bai, Yunhao, additional, Zhu, Bokai, additional, Barrera, Irving, additional, Murray, Evan, additional, Vigneau, Sébastien, additional, Napolitano, Sara, additional, Wakiro, Isaac, additional, Wu, Jingyi, additional, Grimaldi, Grace, additional, Dellostritto, Laura, additional, Helvie, Karla, additional, Rotem, Asaf, additional, Lako, Ana, additional, Cullen, Nicole, additional, Pfaff, Kathleen L., additional, Karlström, Åsa, additional, Jané-Valbuena, Judit, additional, Todres, Ellen, additional, Thorner, Aaron, additional, Geeleher, Paul, additional, Rodig, Scott J., additional, Zhou, Xin, additional, Stewart, Elizabeth, additional, Johnson, Bruce E., additional, Wu, Gang, additional, Chen, Fei, additional, Yu, Jiyang, additional, Goltsev, Yury, additional, Nolan, Garry P., additional, Rozenblatt-Rosen, Orit, additional, Regev, Aviv, additional, and Dyer, Michael A., additional

Published
2024
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49. Biomarkers of pembrolizumab efficacy in advanced anal squamous cell carcinoma: analysis of a phase II clinical trial and a cohort of long-term responders

Author

Huffman, Brandon M, primary, Singh, Harshabad, additional, Ali, Lestat R, additional, Horick, Nora, additional, Wang, S Jennifer, additional, Hoffman, Megan T, additional, Metayer, Katherine A, additional, Murray, Shayla, additional, Bird, Alexandra, additional, Abrams, Thomas A, additional, Biller, Leah H, additional, Chan, Jennifer A, additional, Meyerhardt, Jeffrey A, additional, McCleary, Nadine J, additional, Goessling, Wolfram, additional, Patel, Anuj K, additional, Wisch, Jeffrey S, additional, Yurgelun, Matthew B, additional, Mouw, Kent, additional, Reardon, Brendan, additional, Van Allen, Eliezer M, additional, Zerillo, Jessica A, additional, Clark, Jeffrey W, additional, Parikh, Aparna, additional, Mayer, Robert J, additional, Schlechter, Benjamin, additional, Ng, Kimmie, additional, Kumar, Sunil, additional, Del Vecchio Fitz, Catherine, additional, Kuperwasser, Charlotte, additional, Hanna, Glenn J, additional, Coveler, Andrew L, additional, Rubinson, Douglas A, additional, Welsh, Emma L, additional, Pfaff, Kathleen, additional, Rodig, Scott, additional, Dougan, Stephanie K, additional, and Cleary, James M, additional

Published
2024
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50. Targeting immunosuppressive macrophages overcomes PARP inhibitor resistance in BRCA1-associated triple-negative breast cancer

Author

Mehta, Anita K., Cheney, Emily M., Hartl, Christina A., Pantelidou, Constantia, Oliwa, Madisson, Castrillon, Jessica A., Lin, Jia-Ren, Hurst, Katie E., de Oliveira Taveira, Mateus, Johnson, Nathan T., Oldham, William M., Kalocsay, Marian, Berberich, Matthew J., Boswell, Sarah A., Kothari, Aditi, Johnson, Shawn, Dillon, Deborah A., Lipschitz, Mikel, Rodig, Scott, Santagata, Sandro, Garber, Judy E., Tung, Nadine, Yélamos, José, Thaxton, Jessica E., Mittendorf, Elizabeth A., Sorger, Peter K., Shapiro, Geoffrey I., and Guerriero, Jennifer L.

Published
2021
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