Article
Oncology
Jiakai Hou, Yunfei Wang, Leilei Shi, Yuan Chen, Chunyu Xu, Arash Saeedi, Ke Pan, Ritu Bohat, Nicholas A. Egan, Jodi A. McKenzie, Rina M. Mbofung, Leila J. Williams, Zhenhuang Yang, Ming Sun, Xiaofang Liang, Jordi Rodon Ahnert, Navin Varadarajan, Cassian Yee, Yiwen Chen, Patrick Hwu, Weiyi Peng
Summary: This study used genome-wide CRISPR immune screens to identify immunosuppressive mechanisms in non-responders to cancer immunotherapy and integrated the results with multi-omics clinical data to evaluate the role of tumor intrinsic factors in regulating two key steps of cancer immunotherapy. Two distinct types of immune resistance regulators were revealed, with PRMT1 and RIPK1 identified as potential therapeutic targets to improve the efficacy of immunotherapy. Targeting PRMT1 and RIPK1 sensitized tumors to T-cell killing and anti-PD-1/OX40 treatment, providing novel targets for rational immuno-oncology combinations.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Immunology
Xinting Yang, Jun Yan, Yu Xue, Qing Sun, Yun Zhang, Ru Guo, Chaohong Wang, Xuelian Li, Qingtao Liang, Hangyu Wu, Chong Wang, Xinlei Liao, Sibo Long, Maike Zheng, Rongrong Wei, Haoran Zhang, Yi Liu, Nanying Che, Laurence Don Wai Luu, Junhua Pan, Guirong Wang, Yi Wang
Summary: Using single-cell RNA sequencing, researchers found that tuberculosis pleural effusion (TPE) displayed significant differences in cell types compared to other types of effusion (TSPE and MPE), and these differences were associated with disease type. CD4 lymphocytes in TPE favored a Th1 and Th17 response, and immune exhaustion in NK cells was a prominent feature. Myeloid cells in TPE exhibited stronger functional capacity for phagocytosis, antigen presentation, and IFN-γ response. Additionally, macrophages drove the systemic elevation of inflammatory response genes and pro-inflammatory cytokines in TPE patients.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Siqi Xiong, Wenqiang Zhu, Liqing Wu, Tianmin Zhou, Wu Wang, Ouyang Zhang, Xiaoliang Xiong, Zhuoqi Liu, Daya Luo
Summary: This study identified two distinct circadian rhythm subtypes in breast cancer patients, which have different impacts on the tumor microenvironment and therapeutic response. The high-CR subtype is associated with immunosuppression, poor prognosis, and drug resistance, while the low-CR subtype is associated with high immune cell infiltration, anti-tumor immunity, and sensitivity to immune checkpoint blockade treatment. Therefore, circadian rhythms have potential clinical utility for immunotherapy in breast cancer.
CANCER IMMUNOLOGY IMMUNOTHERAPY
(2023)
Article
Cell Biology
Angel F. Alvarez-Prado, Roeltje R. Maas, Klara Soukup, Florian Klemm, Mara Kornete, Fanny S. Krebs, Vincent Zoete, Sabina Berezowska, Jean-Philippe Brouland, Andreas F. Hottinger, Roy T. Daniel, Monika E. Hegi, Johanna A. Joyce
Summary: Brain metastases (BrMs) are a common type of brain tumor in adults, usually originating from lung and breast primary cancers. Effective therapies are needed due to the high mortality rate associated with BrMs. Genetic profiling of primary tumors is used to guide targeted therapies against BrMs, and immune-based strategies for metastatic cancer treatment are gaining momentum. However, the tumor immune microenvironment (TIME) of BrMs is heterogeneous and it is unknown whether specific genetic profiles are associated with distinct immune states. In this study, the immunogenomic landscape of human BrMs was extensively characterized, revealing unique TIME phenotypes in genetically distinct lung- and breast-BrMs, which allows for the development of personalized immunotherapies based on the genetic makeup of the tumors.
CELL REPORTS MEDICINE
(2023)
Review
Endocrinology & Metabolism
Rachel Weil, David Loeb
Summary: Immunotherapies have had limited success against sarcomas due to factors such as the immunosuppressive tumor microenvironment, lack of predictive biomarkers, decreased T-cell clonal frequency, and high expression of immunosuppressive infiltrating cells. Understanding the individual components of the tumor microenvironment and their interactions within the complex immune microenvironment can lead to more effective immunotherapy treatments and improved outcomes for patients with metastatic disease.
FRONTIERS IN ENDOCRINOLOGY
(2023)
Article
Oncology
Jing Sun, Run Shi, Xiaowen Zhang, Da Fang, Josefine Rauch, Shun Lu, Xuanbin Wang, Lukas Kasmann, Jing Ma, Claus Belka, Chuan Su, Minglun Li
Summary: This study investigated the immune landscape in PTC and established a prognostic immune-related signature (IRS) for predicting progression-free survival (PFS). A survival decision tree and scoring nomogram were constructed to improve prognostic stratification and predictive accuracy. Analysis of altered pathways, mutational patterns, and potential drugs in different immune-related risk groups was also conducted.
Article
Oncology
Chao Zhang, Kai Yin, Si-Yang Liu, Li-Xu Yan, Jian Su, Yi-Long Wu, Xu-Chao Zhang, Wen-Zhao Zhong, Xue-Ning Yang
Summary: For patients with early stage MPLC, neoadjuvant immunotherapy may have varying effects on different tumor nodules due to differences in genomic heterogeneity and immune microenvironment. Additionally, increased infiltration of Trm cells may serve as a unique marker of early immune responses to PD-1 blockade.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2021)
Article
Medicine, Research & Experimental
Zaoqu Liu, Yuyuan Zhang, Chengcheng Shi, Xueliang Zhou, Kaihao Xu, Dechao Jiao, Zhenqiang Sun, Xinwei Han
Summary: The study identified three distinct tumor immunological microenvironment (TIME) phenotypes in hepatocellular carcinoma, each with different clinical outcomes, immune escape mechanisms, and genomic alterations. These findings may offer strategies to improve the efficacy of immunotherapy. Time index (TI) was proposed as a novel prognostic and immunotherapeutic signature to guide personalized immunotherapy and clinical management of HCC.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Article
Immunology
Xiaowu Bai, Weixin Liu, Hongxia Chen, Tao Zuo, Xiaojian Wu
Summary: By analyzing RNA-seq data from patients with IBD (including CD and UC) and healthy individuals, this study revealed increased numbers of immune cells in different intestinal regions and disease-specific immune features in CD and UC. These findings provide important insights into the pathogenesis of IBD and serve as a valuable resource for future targeted studies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Zhao Zhang, Zhijie Zhu, Xincheng Liu, Zhenzhou Mi, Huiren Tao, Hongbin Fan
Summary: This study explores the significance of anoikis-related genes (ANRGs) in osteosarcoma and their impact on the immune landscape. It establishes a prognostic signature based on ANRGs and develops a model for predicting survival probability in osteosarcoma patients. The study also identifies chemotherapeutic agents suitable for different subtypes of osteosarcoma.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Immunology
Mou Peng
Summary: This study aimed to classify immune subtypes and investigate the tumor microenvironment of urothelial carcinoma to improve the understanding and response of immunotherapy. Patients were classified into four immune subtypes with different molecular expression, immune cell infiltration, and clinical characteristics. The C3 immune subtype displayed abundant immune cell infiltrations and hot tumor phenotypes, while the C4 immune subtype had few immune cell infiltrations and cold tumor phenotypes. C3 subtype showed higher expression of tumor mutation burden, inhibitory immune checkpoints, and immunogenic cell death modulators. Patients with the C4 subtype had a better overall survival probability. TGFB3 was identified as a potential biomarker for predicting immunotherapy resistance. This study provides a bioinformatics basis for understanding the immune landscape of urothelial carcinoma.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Immunology
Tao Wang, Tianye Li, Baiqing Li, Jiahui Zhao, Zhi Li, Mingyi Sun, Yan Li, Yanjiao Zhao, Shidi Zhao, Weiguang He, Xiao Guo, Rongjing Ge, Lian Wang, Dushan Ding, Saisai Liu, Simin Min, Xiaonan Zhang
Summary: Breast cancer has different immune subtypes with diverse characteristics and clinical prognostications. Patients with a high immunotherapeutic benefit score (ITBscore) have better response to immunotherapy, while those with a low ITBscore have poor immunotherapeutic efficacy. This study provides insights into the immune phenotypes in the tumor microenvironment and guides precision immuno-oncology and immunotherapy strategies.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Xiaoyu Yang, Bo Song, Jie Cui, Lina Wang, Shuoshuo Wang, Linlin Luo, Lei Gao, Beixin Mo, Yu Yu, Lin Liu
Summary: This study reveals that translational reprogramming plays an important role in rice's response to salt stress, with the salt-tolerant cultivar SR86 adopting a more flexible translational adaptive strategy compared to the salt-sensitive cultivar NB. The differences in translational dynamics under salt stress between NB and SR86 may be due to their varying levels of ribosome stalling.
Article
Oncology
Jinfang Liu, Rong Ma, Siyuan Chen, Yongxian Lai, Guangpeng Liu
Summary: In this study, a prognostic signature related to Anoikis was established using DEGs analysis. It was found that low-risk patients showed low immune cell infiltration, high immunoscores and immune checkpoint expression, and increased sensitivity to various drugs.
CLINICAL & TRANSLATIONAL ONCOLOGY
(2023)
Article
Oncology
Qing Zhang, Yongkun Yang, Xia You, Yongzhi Ju, Qin Zhang, Tingting Sun, Weifeng Liu
Summary: Bone sarcoma and soft tissue sarcoma have significantly different clinical and molecular characteristics. This study aimed to analyze the genomic landscapes and actionable genomic alterations of Chinese patients with primary bone sarcomas and STS. The results showed that TP53, CDKN2A, CDKN2B, MAP3K1, LRP1B, MDM2, RB1, PTEN, MYC, and CDK4 were frequently altered genes in both types of sarcomas.
FRONTIERS IN ONCOLOGY
(2023)
Review
Pathology
Joseph G. Schroers-Martin, Stefan Alig, Andrea Garofalo, Benoit Tessoulin, Takeshi Sugio, Ash A. Alizadeh
Summary: Molecular monitoring plays a crucial role in the surveillance and clinical management of lymphomas, aided by the high concentration of cell-free DNA and circulating tumor DNA, high somatic mutational burden, and presence of recurrently altered regions. This review summarizes the current evidence on molecular subtyping, classification, treatment response evaluation, surveillance of cellular therapies, and emerging clinical trial strategies for lymphomas.
ANNUAL REVIEW OF PATHOLOGY-MECHANISMS OF DISEASE
(2023)
Article
Oncology
Rutulkumar Patel, Yvonne M. Mowery, Yi Qi, Alex M. Bassil, Matt Holbrook, Eric S. Xu, Cierra S. Hong, Jonathon E. Himes, Nerissa T. Williams, Jeffrey Everitt, Yan Ma, Lixia Luo, Sara R. Selitsky, Jennifer L. Modliszewski, Junheng Gao, Sin -Ho Jung, David G. Kirsch, Cristian T. Badea
Summary: This study aims to investigate the effect of adding neoadjuvant radiotherapy and anti-PD-1 therapy to surgical resection on disease-free survival for mice with soft tissue sarcomas. The results showed that the combination of anti-PD-1, radiotherapy, and surgery improved local recurrence-free survival and disease-free survival. However, only radiotherapy, not anti-PD-1, significantly improved local recurrence-free survival and metastasis-free survival. The study also found that sarcoma metastasis is regulated by both immunosurveillance and tumor cell-intrinsic mechanisms.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Pathology
Stephanie J. Blocker, Samantha Morrison, Jeffrey I. Everitt, James Cook, Sheng Luo, Tammara L. Watts, Yvonne M. Mowery
Summary: This study utilized automated image analysis techniques in whole-slide images of HNSCC tumors to identify relationships between cytometric features and genomic phenotypes. The study found significant associations between cytometric features and integrated genomic subtype, particularly in distinguishing the basal subtype from the chromosomal instability and immune subtypes based on cytometric feature measurements.
AMERICAN JOURNAL OF PATHOLOGY
(2023)
Article
Oncology
Brian J. Sworder, David M. Kurtz, Stefan K. Alig, Matthew J. Frank, Navika Shukla, Andrea Garofalo, Charles W. Macaulay, Mohammad Shahrokh Esfahani, Mari N. Olsen, James Hamilton, Hitomi Hosoya, Mark Hamilton, Jay Y. Spiegel, John H. Baird, Takeshi Sugio, Mia Carleton, Alexander F. M. Craig, Sheren F. Younes, Bita Sahaf, Natasha D. Sheybani, Joseph G. Schroers-Martin, Chih Long Liu, Jean S. Oak, Michael C. Jin, Sara Beygi, Andreas Huttmann, Christine Hanoun, Ulrich Duhrsen, Jason R. Westin, Michael S. Khodadoust, Yasodha Natkunam, Robbie G. Majzner, Crystal L. Mackall, Maximilian Diehn, David B. Miklos, Ash A. Alizadeh
Summary: This study investigates the resistance of anti-CD19 chimeric antigen receptor (CAR19) T cells in relapsed/refractory large B-cell lymphoma (r/rLBCL) patients. By analyzing longitudinal samples from two independent cohorts, it identifies multiple gene alterations associated with resistance, such as B cell identity genes (PAX5 and IRF8), immune checkpoint genes (CD274), and genes affecting the tumor microenvironment (TMEM30A). It also reveals that somatic tumor alterations affect CAR19 therapy at various levels, including CAR19 T cell expansion, persistence, and tumor microenvironment. These findings have implications for improving CAR T cells and personalized therapeutic approaches.
Article
Hematology
Hua-Jay J. Cherng, Stefan K. Alig, Yasuhiro Oki, Loretta J. Nastoupil, Luis Fayad, Sattva S. Neelapu, Francesco Turturro, Fredrick Hagemeister, Alexander F. M. Craig, Charles W. Macaulay, Maria Alma Rodriguez, Hun Ju Lee, Timothy J. McDonnell, Christopher R. Flowers, Francisco Vega, Michael R. Green, Lei Feng, David M. Kurtz, Ash A. Alizadeh, R. Eric Davis, Jason R. Westin
Summary: LO-CHOP treatment shows high efficacy and tolerability in newly diagnosed DLBCL, leading to a high rate of overall and complete response. It is a potentially effective and well-tolerated treatment option.
Article
Oncology
Justin M. Barnes, Evan M. Graboyes, Eric Adjei Boakye, Mario Schootman, Junzo P. Chino, Haley A. Moss, Yvonne M. Mowery, Nosayaba Osazuwa-Peters
Summary: The purpose of this study was to assess insurance coverage and forgoing medical care due to cost in cancer survivors from 2016 to 2019. The results showed that the number of insured cancer survivors decreased by 161,000 and there was an increase of 169,000 in those forgoing medical care due to cost. The most significant impact was observed among low-income individuals and those residing in non-expansion states.
JCO ONCOLOGY PRACTICE
(2023)
Article
Hematology
Ryan C. Lynch, Chaitra S. Ujjani, Christina Poh, Edus H. Warren, Stephen D. Smith, Mazyar Shadman, Brian Till, Vikram M. Raghunathan, Stefan Alig, Ash A. Alizadeh, Avanti Gulhane, Delphine L. Chen, Yolanda Tseng, Hilary Coye, Megan Shelby, Susan Ottemiller, Sarith Keo, Kaitlin Verni, Hongyan Du, Jacquelin Vandermeer, Ashley Gaston, Heather Rasmussen, Paul Martin, Edmond Marzbani, Jenna Voutsinas, Ajay K. Gopal
Summary: This study investigated the concurrent administration of pembrolizumab with chemotherapy in untreated classic Hodgkin lymphoma, showing promising safety and efficacy. Although some patients experienced adverse events, the overall response rate was 100% with a complete response rate of 90%.
Review
Biochemistry & Molecular Biology
Kyle Swanson, Eric Wu, Angela Zhang, Ash A. Alizadeh, James Zou
Summary: Machine learning is increasingly used in clinical oncology to diagnose cancers, predict patient outcomes, and inform treatment planning. This review focuses on recent applications of machine learning across the clinical oncology workflow, including medical imaging and molecular data obtained from liquid and solid tumor biopsies for cancer diagnosis, prognosis, and treatment design. Key considerations in developing machine learning for the distinct challenges posed by imaging and molecular data are discussed. The review also examines machine learning models approved for cancer-related patient usage by regulatory agencies and discusses approaches to improve the clinical usefulness of machine learning.
Article
Oncology
Divya Natesan, Christina K. Cramer, Taofik Oyekunle, Donna Niedzwiecki, David M. Brizel, Yvonne M. Mowery
Summary: The study suggests that ipsilateral neck radiotherapy (IRT) may be an effective treatment for tonsillar squamous cell carcinoma (SCC) with multiple involved ipsilateral nodes, especially when baseline staging is performed with PET/CT.
Article
Hematology
Patricia Johansson, Stefan Alig, Julia Richter, Christine Hanoun, Jan Rekowski, Jan Duerig, Bauke Ylstra, Daphne de Jong, Wolfram Klapper, Ash A. Alizadeh, Ulrich Duehrsen, Andreas Huettmann
Summary: In DLBCL, a positive interim PET scan predicts treatment failure, and combining it with the presence of an IgM gammopathy can improve prediction. The combination of interim PET and IgM gammopathy can dichotomize the population into high-risk and low-risk groups with significantly different outcomes. Only the interim PET result and IgM gammopathy status were significantly associated with outcome, making them important factors in risk-adapted treatment strategies.
ANNALS OF HEMATOLOGY
(2023)
Editorial Material
Oncology
Yvonne M. Mowery
INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS
(2023)
Article
Radiology, Nuclear Medicine & Medical Imaging
Ashlyn G. Rickard, Yvonne M. Mowery, Alex Bassil, Douglas C. Rouse, Nerissa T. Williams, Theresa Charity, Rafaela Belloni, Brian Crouch, Nimmi Ramanujam, Daniel Stevenson, Rico Castillo, Stephanie Blocker, Boris Epel, Mrignayani Kotecha, Gregory M. Palmer
Summary: Tumor hypoxia, which is less sensitive to radiation therapy, is a major obstacle in cancer treatment. This study investigated the use of EPROI imaging to quantify tumor oxygenation and assessed the impact of the mitochondrial inhibitor PPV on hypoxia and radiation response in two mouse tumor models. The results showed that hypoxic sarcomas were more radioresistant, and PPV did not sensitize tumors to radiation in both models.
MOLECULAR IMAGING AND BIOLOGY
(2023)
Article
Oncology
Eliza M. Lauer, Ella Riegler, Jurik A. Mutter, Stefan K. Alig, Sabine Bleul, Julia Kuehn, Lavanya Ranganathan, Christian Klingler, Theo Demerath, Urs Wuertemberger, Alexander Rau, Jakob Weiss, Michel Eisenblaetter, Fabian Bamberg, Marco Prinz, Juergen Finke, Justus Duyster, Gerald Illerhaus, Maximilian Diehn, Ash A. Alizadeh, Elisabeth Schorb, Peter C. Reinacher, Florian Scherer
Summary: The study found that the use of semi-automated three-dimensional tumor volume measurements can serve as strong and independent early predictors of clinical outcomes in central nervous system lymphoma (CNSL) patients. These radiologic features can help improve risk stratification and guide future treatment approaches.
Article
Endocrinology & Metabolism
Amy J. Wisdom, M. Aiven Dyer, Nora K. Horick, Beow. Y. Yeap, Karen K. Miller, Brooke Swearingen, Jay S. Loeffler, Helen A. Shih
Summary: The purpose of this study was to investigate the impact of multidisciplinary treatment on the quality of life (QoL) of patients with nonfunctioning pituitary macroadenomas (NFPMA). The findings showed that radiation therapy after transsphenoidal surgery (TSS), hypopituitarism, and financial stressors were associated with impaired QoL in patients with NFPMA.
Article
Medicine, Research & Experimental
Min Yao, Jonathan Preall, Johannes T. -H. Yeh, Darryl Pappin, Paolo Cifani, Yixin Zhao, Sophia Shen, Philip Moresco, Brian He, Hardik Patel, Amber N. Habowski, Daniel A. King, Kara Raphael, Arvind Rishi, Divyesh Sejpal, Matthew J. Weiss, David Tuveson, Douglas T. Fearon
Summary: Intratumoral B cell responses are associated with better clinical outcomes in human pancreatic ductal adenocarcinoma (PDAC). This study used single-cell RNA sequencing and immunoglobulin sequencing to identify the antigens driving these responses in PDAC samples. The researchers observed activated T and B cell responses and evidence of germinal center reactions. They also found that PDAC patients produce autoantibodies reacting with intracellular self-antigens, which may result from preexisting autoreactive B cell responses. These findings suggest that the chronic inflammatory microenvironment of PDAC can support the adaptive immune response.