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Nov 2022 • Blood

Ipilimumab plus decitabine for patients with MDS or AML in post-transplant or transplant naïve settings

Jacqueline S Garcia, Yael Flamand, Livius Penter, Michael Keng, Benjamin K Tomlinson, Lourdes M Mendez, Paul Koller, Nicole Cullen, Yohei Arihara, Kathleen Pfaff, Jacquelyn O Wolff, Andrew M Brunner, Ilene Galinsky, Asad Bashey, Joseph H Antin, Corey Cutler, Vincent Ho, Brian A Jonas, Marlise R Luskin, Martha Wadleigh, Eric S Winer, Alexandra Savell, Rebecca Leonard, Taylor Robertson, Matthew S Davids, Howard Streicher, Scott J Rodig, Jerome Ritz, Catherine J Wu, Daniel J DeAngelo, Donna Neuberg, Richard M Stone, Robert J Soiffer

Ipilimumab monotherapy has clinical activity in patients with acute myeloid leukemia (AML) who relapse after allogeneic hematopoietic stem cell transplant (HSCT) when disease burden is low. We hypothesized that ipilimumab-driven responses required alloreactivity and the addition of decitabine could augment responses without generating excessive toxicity. We conducted a multicenter phase 1 trial of ipilimumab and decitabine (IPI+ DEC) in relapsed, refractory or secondary untreated MDS/AML (CTEP10026; NCT02890329) with patients stratified by transplant status. Patients received a lead-in cycle of decitabine followed by combination therapy with IPI (3, 5, or 10 mg/kg) every 4 weeks for four cycles and then every 8 weeks for up to eight cycles. In total, 48 patients received IPI+ DEC (25 post-HSCT, 23 transplant naïve). In the post-HSCT cohort, 36%(9/25) experienced immune-related adverse events (irAEs …

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Oct 2022 • Science Advances

Machine learning on syngeneic mouse tumor profiles to model clinical immunotherapy response

Zexian Zeng, Shengqing Stan Gu, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Myles Brown, X Shirley Liu

Most patients with cancer are refractory to immune checkpoint blockade (ICB) therapy, and proper patient stratification remains an open question. Primary patient data suffer from high heterogeneity, low accessibility, and lack of proper controls. In contrast, syngeneic mouse tumor models enable controlled experiments with ICB treatments. Using transcriptomic and experimental variables from >700 ICB-treated/control syngeneic mouse tumors, we developed a machine learning framework to model tumor immunity and identify factors influencing ICB response. Projected on human immunotherapy trial data, we found that the model can predict clinical ICB response. We further applied the model to predicting ICB-responsive/resistant cancer types in The Cancer Genome Atlas, which agreed well with existing clinical reports. Last, feature analysis implicated factors associated with ICB response. In summary, our …

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Sep 2022 • Nucleic Acids Research

TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response

Zexian Zeng, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Shengqing Gu, Yi Zhang, Yang Liu, Xiaoqing Wang, Jingxin Fu, Liye Zhou, Boning Zhang, Sarah Kim, Kathleen B Yates, Myles Brown, Gordon J Freeman, Ravindra Uppaluri, Robert Manguso, X Shirley Liu

Syngeneic mouse models are tumors derived from murine cancer cells engrafted on genetically identical mouse strains. They are widely used tools for studying tumor immunity and immunotherapy response in the context of a fully functional murine immune system. Large volumes of syngeneic mouse tumor expression profiles under different immunotherapy treatments have been generated, although a lack of systematic collection and analysis makes data reuse challenging. We present Tumor Immune Syngeneic MOuse (TISMO), a database with an extensive collection of syngeneic mouse model profiles with interactive visualization features. TISMO contains 605 in vitro RNA-seq samples from 49 syngeneic cancer cell lines across 23 cancer types, of which 195 underwent cytokine treatment. TISMO also includes 1518 in vivo RNA-seq samples from 68 syngeneic mouse tumor models across 19 cancer types, of …

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Sep 2022 • Cancer Immunology Research

Immune phenotypes and target antigens of clonally expanded bone marrow T cells in treatment-naïve multiple myeloma

Carlotta Welters, Lammoglia Cobo MF, Christian Alexander Stein, Meng Tung Hsu, L Penter, X Chen, C Buccitelli, O Popp, P Mertins, K Dietze, L Bullinger, A Moosmann, E Blanc, D Beule, A Gerbitz, J Strobel, H Hackstein, HP Rahn, K Dornmair, T Blankenstein, L Hansmann


Sep 2022 • Blood, The Journal of the American Society of Hematology

AML relapse after a TIGIT race

Livius Penter, Catherine J Wu

In this issue of Blood, Gournay et al 1 dissect donor immune reconstitution after allogeneic hematopoietic stem cell transplantation (HSCT) with mass cytometry and identify T-cell immunoreceptor with Ig and ITIM domains (TIGIT) and CD161-expressing CD4+ T cells as early immune correlates of subsequent acute myelogenous leukemia (AML) relapse after HSCT.The high relapse rate of AML after stem cell transplant has remained one of the most tenacious problems in malignant hematology. With the graft-versusleukemia (GVL) effect at the core of successful long-term disease control, the early posttransplant course can be thought of as a delicate race between nascent donor immune reconstitution and recovering malignant cell populations that seek to escape GVL. AML relapse after HSCT thus often associates with donor immune cell dysfunction through upregulated immune checkpoint molecules or reduced …

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Sep 2022 • Nature Methods

MIRA: joint regulatory modeling of multimodal expression and chromatin accessibility in single cells

Allen W Lynch, Christina V Theodoris, Henry W Long, Myles Brown, X Shirley Liu, Clifford A Meyer

Rigorously comparing gene expression and chromatin accessibility in the same single cells could illuminate the logic of how coupling or decoupling of these mechanisms regulates fate commitment. Here we present MIRA, probabilistic multimodal models for integrated regulatory analysis, a comprehensive methodology that systematically contrasts transcription and accessibility to infer the regulatory circuitry driving cells along cell state trajectories. MIRA leverages topic modeling of cell states and regulatory potential modeling of individual gene loci. MIRA thereby represents cell states in an efficient and interpretable latent space, infers high-fidelity cell state trees, determines key regulators of fate decisions at branch points and exposes the variable influence of local accessibility on transcription at distinct loci. Applied to epidermal differentiation and embryonic brain development from two different multimodal …

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Jul 2022 • Cancer immunology research

Comprehensive characterizations of immune receptor repertoire in tumors and cancer immunotherapy studies

Li Song, Zhangyi Ouyang, David Cohen, Yang Cao, Jennifer Altreuter, Gali Bai, Xihao Hu, Kenneth J Livak, Heng Li, Ming Tang, Bo Li, X Shirley Liu

We applied our computational algorithm TRUST4 to assemble immune receptor (T-cell receptor/B-cell receptor) repertoires from approximately 12,000 RNA sequencing samples from The Cancer Genome Atlas and seven immunotherapy studies. From over 35 million assembled complete complementary-determining region 3 sequences, we observed that the expression of CCL5 and MZB1 is the most positively correlated genes with T-cell clonal expansion and B-cell clonal expansion, respectively. We analyzed amino acid evolution during B-cell receptor somatic hypermutation and identified tyrosine as the preferred residue. We found that IgG1+IgG3 antibodies together with FcRn were associated with complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity or phagocytosis. In addition to B-cell infiltration, we discovered that B-cell clonal expansion and IgG1+IgG3 …

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Jun 2022 • Cancer Research

Immune population changes in mammary adipose tissue during the development of obesity and their influence on triple negative breast cancer progression

Shimeng Liu, Yi Zhang, Myles Brown

Obesity is associated with increased risk for many cancer types, including triple-negative breast cancer (TNBC). In addition to obesity’s role in TNBC pathogenesis, it is also recognized as a marker of poor prognosis for survival in pre- and post-menopausal women. However, the mechanism underlying how obesity leads to worsened TNBC progression remains unclear. In this study, we aim to characterize the immune population changes in mammary adipose during the development of obesity and their impact on TNBC progression. First, we utilized a diet-induced obesity mouse model to evaluate tumor growth under obese condition. Four weeks after E0771 (TNBC cell line) mammary fat pad injection, TNBC tumors volume were 1.6-fold larger in obese C57BL/6 mice compared to their lean counterparts. To profile the transcriptome changes induced by obesity, we performed single-cell RNA-Seq on mammary …

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May 2022 • Clinical Cancer Research

Immunostimulatory cancer-associated fibroblast subpopulations can predict immunotherapy response in head and neck cancer

Aleksandar Obradovic, Diana Graves, Michael Korrer, Yu Wang, Sohini Roy, Abdullah Naveed, Yaomin Xu, Adam Luginbuhl, Joseph Curry, Michael Gibson, Kamran Idrees, Paula Hurley, Peng Jiang, X Shirley Liu, Ravindra Uppaluri, Charles G Drake, Andrea Califano, Young J Kim

Purpose Cancer-associated fibroblasts (CAF) have been implicated as potential mediators of checkpoint immunotherapy response. However, the extensive heterogeneity of these cells has precluded rigorous understanding of their immunoregulatory role in the tumor microenvironment. Experimental Design We performed high-dimensional single-cell RNA sequencing (scRNA-seq) on four patient tumors pretreatment and posttreatment from a neoadjuvant trial of patients with advanced-stage head and neck squamous cell carcinoma that were treated with the αPD-1 therapy, nivolumab. The head and neck CAF (HNCAF) protein activity profiles, derived from this cohort of paired scRNA-seq, were used to perform protein activity enrichment analysis on the 28-patient parental cohort of clinically annotated bulk transcriptomic profiles. Ex vivo coculture assays were used to test …

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May 2022 • Cell

Topical therapy for regression and melanoma prevention of congenital giant nevi

Yeon Sook Choi, Tal H Erlich, Max von Franque, Inbal Rachmin, Jessica L Flesher, Erik B Schiferle, Yi Zhang, Marcello Pereira da Silva, Alva Jiang, Allison S Dobry, Mack Su, Sharon Germana, Sebastian Lacher, Orly Freund, Ezra Feder, Jose L Cortez, Suyeon Ryu, Tamar Babila Propp, Yedidyah Leo Samuels, Labib R Zakka, Marjan Azin, Christin E Burd, Norman E Sharpless, X Shirley Liu, Clifford Meyer, William Gerald Austen Jr, Branko Bojovic, Curtis L Cetrulo Jr, Martin C Mihm, Dave S Hoon, Shadmehr Demehri, Elena B Hawryluk, David E Fisher

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate …

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May 2022 • Cell

Topical therapy for regression and melanoma prevention of congenital giant nevi

Yeon Sook Choi, Tal H Erlich, Max von Franque, Inbal Rachmin, Jessica L Flesher, Erik B Schiferle, Yi Zhang, Marcello Pereira da Silva, Alva Jiang, Allison S Dobry, Mack Su, Sharon Germana, Sebastian Lacher, Orly Freund, Ezra Feder, Jose L Cortez, Suyeon Ryu, Tamar Babila Propp, Yedidyah Leo Samuels, Labib R Zakka, Marjan Azin, Christin E Burd, Norman E Sharpless, X Shirley Liu, Clifford Meyer, William Gerald Austen Jr, Branko Bojovic, Curtis L Cetrulo Jr, Martin C Mihm, Dave S Hoon, Shadmehr Demehri, Elena B Hawryluk, David E Fisher

Giant congenital melanocytic nevi are NRAS-driven proliferations that may cover up to 80% of the body surface. Their most dangerous consequence is progression to melanoma. This risk often triggers preemptive extensive surgical excisions in childhood, producing severe lifelong challenges. We have presented preclinical models, including multiple genetically engineered mice and xenografted human lesions, which enabled testing locally applied pharmacologic agents to avoid surgery. The murine models permitted the identification of proliferative versus senescent nevus phases and treatments targeting both. These nevi recapitulated the histologic and molecular features of human giant congenital nevi, including the risk of melanoma transformation. Cutaneously delivered MEK, PI3K, and c-KIT inhibitors or proinflammatory squaric acid dibutylester (SADBE) achieved major regressions. SADBE triggered innate …

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May 2022 • Nature cancer

IKAROS and MENIN coordinate therapeutically actionable leukemogenic gene expression in MLL-r acute myeloid leukemia

Brandon J Aubrey, Jevon A Cutler, Wallace Bourgeois, Katherine A Donovan, Shengqing Gu, Charlie Hatton, Sarah Perlee, Florian Perner, Homa Rahnamoun, Alexandra CP Theall, Jill A Henrich, Qian Zhu, Radosław P Nowak, Young Joon Kim, Salma Parvin, Anjali Cremer, Sarah Naomi Olsen, Nicholas A Eleuteri, Yana Pikman, Gerard M McGeehan, Kimberly Stegmaier, Anthony Letai, Eric S Fischer, X Shirley Liu, Scott A Armstrong

Acute myeloid leukemia (AML) remains difficult to treat and requires new therapeutic approaches. Potent inhibitors of the chromatin-associated protein MENIN have recently entered human clinical trials, opening new therapeutic opportunities for some genetic subtypes of this disease. Using genome-scale functional genetic screens, we identified IKAROS (encoded by IKZF1) as an essential transcription factor in KMT2A (MLL1)-rearranged (MLL-r) AML that maintains leukemogenic gene expression while also repressing pathways for tumor suppression, immune regulation and cellular differentiation. Furthermore, IKAROS displays an unexpected functional cooperativity and extensive chromatin co-occupancy with mixed lineage leukemia (MLL)1–MENIN and the regulator MEIS1 and an extensive hematopoietic transcriptional complex involving homeobox (HOX)A10, MEIS1 and IKAROS. This dependency could be …

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May 2022 • Cytotherapy

Rapid single-cell identification of Epstein–Barr virus-specific T-cell receptors for cellular therapy

María Fernanda Lammoglia Cobo, Carlotta Welters, Leonie Rosenberger, Matthias Leisegang, Kerstin Dietze, Christian Pircher, Livius Penter, Regina Gary, Lars Bullinger, Anna Takvorian, Andreas Moosmann, Klaus Dornmair, Thomas Blankenstein, Thomas Kammertöns, Armin Gerbitz, Leo Hansmann

Background and aimsEpstein–Barr virus (EBV) is associated with solid and hematopoietic malignancies. After allogeneic stem cell transplantation, EBV infection or reactivation represents a potentially life-threatening condition with no specific treatment available in clinical routine. In vitro expansion of naturally occurring EBV-specific T cells for adoptive transfer is time-consuming and influenced by the donor's T-cell receptor (TCR) repertoire and requires a specific memory compartment that is non-existent in seronegative individuals.The authors present highly efficient identification of EBV-specific TCRs that can be expressed on human T cells and recognize EBV-infected cells.Methods and ResultsMononuclear cells from six stem cell grafts were expanded in vitro with three HLA-B*35:01- or four HLA-A*02:01-presented peptides derived from six EBV proteins expressed during latent and lytic infection. Epitope-specific …

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May 2022 • Cytotherapy

Rapid single-cell identification of Epstein–Barr virus-specific T-cell receptors for cellular therapy

María Fernanda Lammoglia Cobo, Carlotta Welters, Leonie Rosenberger, Matthias Leisegang, Kerstin Dietze, Christian Pircher, Livius Penter, Regina Gary, Lars Bullinger, Anna Takvorian, Andreas Moosmann, Klaus Dornmair, Thomas Blankenstein, Thomas Kammertöns, Armin Gerbitz, Leo Hansmann

Background and aimsEpstein–Barr virus (EBV) is associated with solid and hematopoietic malignancies. After allogeneic stem cell transplantation, EBV infection or reactivation represents a potentially life-threatening condition with no specific treatment available in clinical routine. In vitro expansion of naturally occurring EBV-specific T cells for adoptive transfer is time-consuming and influenced by the donor's T-cell receptor (TCR) repertoire and requires a specific memory compartment that is non-existent in seronegative individuals.The authors present highly efficient identification of EBV-specific TCRs that can be expressed on human T cells and recognize EBV-infected cells.Methods and ResultsMononuclear cells from six stem cell grafts were expanded in vitro with three HLA-B*35:01- or four HLA-A*02:01-presented peptides derived from six EBV proteins expressed during latent and lytic infection. Epitope-specific …

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Apr 2022 • Clinical Cancer Research: an Official Journal of the American Association for Cancer Research

Improved T cell immunity following neoadjuvant chemotherapy in ovarian cancer.

Min Liu, Nabihah Tayob, Livius Penter, M Sellars, Anna Tarren, Vipheaviny Chea, Isabel Carulli, Teddy Huang, Shuqiang Li, Su-Chun Cheng, Phuong Le, Laura Frackiewicz, Julia Fasse, Courtney Qi, Joyce F Liu, Elizabeth H Stover, Jennifer Curtis, Kenneth J Livak, Donna Neuberg, Guang Lan Zhang, Ursula A Matulonis, Catherine J Wu, Derin B Keskin, Panagiotis A Konstantinopoulos

PurposeAlthough local tissue-based immune responses are critical for elucidating direct tumor-immune cell interactions, peripheral immune responses are increasingly recognized as occupying an important role in anti-cancer immunity. We evaluated serial blood samples from patients with epithelial ovarian cancer (EOC) undergoing standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy (including dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reactions) to characterize the evolution of the peripheral immune cell function and composition during therapy.

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Apr 2022 • Clinical Cancer Research: an Official Journal of the American Association for Cancer Research

Improved T cell immunity following neoadjuvant chemotherapy in ovarian cancer.

Min Liu, Nabihah Tayob, Livius Penter, M Sellars, Anna Tarren, Vipheaviny Chea, Isabel Carulli, Teddy Huang, Shuqiang Li, Su-Chun Cheng, Phuong Le, Laura Frackiewicz, Julia Fasse, Courtney Qi, Joyce F Liu, Elizabeth H Stover, Jennifer Curtis, Kenneth J Livak, Donna Neuberg, Guang Lan Zhang, Ursula A Matulonis, Catherine J Wu, Derin B Keskin, Panagiotis A Konstantinopoulos

PurposeAlthough local tissue-based immune responses are critical for elucidating direct tumor-immune cell interactions, peripheral immune responses are increasingly recognized as occupying an important role in anti-cancer immunity. We evaluated serial blood samples from patients with epithelial ovarian cancer (EOC) undergoing standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy (including dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reactions) to characterize the evolution of the peripheral immune cell function and composition during therapy.

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Apr 2022 • Clinical Cancer Research: an Official Journal of the American Association for Cancer Research

Improved T-cell immunity following neoadjuvant chemotherapy in ovarian cancer

Min Liu, Nabihah Tayob, Livius Penter, M Sellars, Anna Tarren, Vipheaviny Chea, Isabel Carulli, Teddy Huang, Shuqiang Li, Su-Chun Cheng, Phuong Le, Laura Frackiewicz, Julia Fasse, Courtney Qi, Joyce F Liu, Elizabeth H Stover, Jennifer Curtis, Kenneth J Livak, Donna Neuberg, Guang Lan Zhang, Ursula A Matulonis, Catherine J Wu, Derin B Keskin, Panagiotis A Konstantinopoulos

PurposeAlthough local tissue-based immune responses are critical for elucidating direct tumor-immune cell interactions, peripheral immune responses are increasingly recognized as occupying an important role in anti-cancer immunity. We evaluated serial blood samples from patients with epithelial ovarian cancer (EOC) undergoing standard-of-care neoadjuvant carboplatin and paclitaxel chemotherapy (including dexamethasone for prophylaxis of paclitaxel-associated hypersensitivity reactions) to characterize the evolution of the peripheral immune cell function and composition during therapy.

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Mar 2022 • Immunity

A high-resolution view of intra-tumoral B cell immunity

Xihao Hu, X Shirley Liu

In this issue of Immunity, Meylan et al. (2022) uses spatial transcriptomics to examine B cell immunity within intratumoral tertiary lymphoid structures (TLSs). They find that B cells expand and mature into plasma cells (PCs) within the TLS, migrate along fibroblastic tracks to tumor beds, and produce IgG antibodies that target cancer cells.

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Jan 2022 • bioRxiv

A Community Challenge to Predict Clinical Outcomes After Immune Checkpoint Blockade in Non-Small Cell Lung Cancer

Michael Mason, Oscar Lapuente-Santana, Anni S Halkola, Wenyu Wang, Raghvendra Mall, Xu Xiao, Jacob Kaufman, Jingxin Fu, Jacob Pfeil, Jineta Banerjee, Verena Chung, Han Chang, Scott D Chasalow, Hung Ying Lin, Rongrong Chai, Thomas Yu, Francesca Finotello, Tuomas Mirtti, Mikko I Mayranpaa, Jie Bao, Emmy W Verschuren, Eiman I Ahmed, Michele Ceccarelli, Lance D Miller, Gianni Monaco, Wouter RL Hendrickx, Shimaa Sherif, Lin Yang, Ming Tang, Shengqing Stan Gu, Wubing Zhang, Yi Zhang, Zexian Zeng, Avinash Das Sahu, Yang Liu, Wenxian Yang, Davide Bedognetti, Jing Tang, Federica Eduati, Teemu D Laajala, William J Geese, Justin Guinney, Joseph D Szustakowski, David P Carbone, Benjamin G Vincent

Purpose: Predictive biomarkers of immune checkpoint inhibitors (ICIs) efficacy are currently lacking for non-small cell lung cancer (NSCLC). Here, we describe the results from the Anti-PD-1 Response Prediction DREAM Challenge, a crowdsourced initiative that enabled the assessment of predictive models by using data from two randomized controlled clinical trials (RCTs) of ICIs in first-line metastatic NSCLC. Methods: Participants developed and trained models using public resources. These were evaluated with data from the CheckMate 026 trial (NCT02041533), according to the model-to-data paradigm to maintain patient confidentiality. The generalizability of the models with the best predictive performance was assessed using data from the CheckMate 227 trial (NCT02477826). Both trials were phase III RCTs with a chemotherapy control arm, which supported the differentiation between predictive and prognostic models. Isolated model containers were evaluated using a bespoke strategy that considered the challenges of handling transcriptome data from clinical trials. Results: A total of 59 teams participated, with 417 models submitted. Multiple predictive models, as opposed to a prognostic model, were generated for predicting overall survival, progression-free survival, and progressive disease status with ICIs. Variables within the models submitted by participants included tumor mutational burden (TMB), programmed death ligand 1 (PD-L1) expression, and gene-expression-based signatures. The best-performing models showed improved predictive power over reference variables, including TMB or PD-L1. Conclusion: This DREAM …

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Jan 2022 • bioRxiv

Machine learning modeling of protein-intrinsic features predicts tractability of targeted protein degradation

Wubing Zhang, Shourya S Roy Burman, Jiaye Chen, Katherine A Donovan, Yang Cao, Boning Zhang, Zexian Zeng, Yi Zhang, Dian Li, Eric S Fischer, Collin Tokheim, Xiaole Shirley Liu

Targeted protein degradation (TPD) has rapidly emerged as a therapeutic modality to eliminate previously undruggable proteins by repurposing the cell’s endogenous protein degradation machinery. However, the susceptibility of proteins for targeting by TPD approaches, termed “degradability”, is largely unknown. Here, we developed a machine learning model, model-free analysis of protein degradability (MAPD), to predict degradability from features intrinsic to protein targets. MAPD shows accurate performance in predicting kinases that are degradable by TPD compounds [with an area under precision recall curve (AUPRC) of 0.759 and area under the receiver operating characteristic curve (AUROC) of 0.775] and is likely generalizable to independent non-kinase proteins. We found five features with statistical significance to achieve optimal prediction, with ubiquitination potential being the most predictive. By …

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Jan 2022 • Nucleic acids research

TISMO: syngeneic mouse tumor database to model tumor immunity and immunotherapy response

Zexian Zeng, Cheryl J Wong, Lin Yang, Nofal Ouardaoui, Dian Li, Wubing Zhang, Shengqing Gu, Yi Zhang, Yang Liu, Xiaoqing Wang, Jingxin Fu, Liye Zhou, Boning Zhang, Sarah Kim, Kathleen B Yates, Myles Brown, Gordon J Freeman, Ravindra Uppaluri, Robert Manguso, X Shirley Liu

Syngeneic mouse models are tumors derived from murine cancer cells engrafted on genetically identical mouse strains. They are widely used tools for studying tumor immunity and immunotherapy response in the context of a fully functional murine immune system. Large volumes of syngeneic mouse tumor expression profiles under different immunotherapy treatments have been generated, although a lack of systematic collection and analysis makes data reuse challenging. We present Tumor Immune Syngeneic MOuse (TISMO), a database with an extensive collection of syngeneic mouse model profiles with interactive visualization features. TISMO contains 605 in vitro RNA-seq samples from 49 syngeneic cancer cell lines across 23 cancer types, of which 195 underwent cytokine treatment. TISMO also includes 1518 in vivo RNA-seq samples from 68 syngeneic mouse tumor models across 19 cancer types, of …

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