Review
Cell Biology
Yasmin Abaza, Amer M. Zeidan
Summary: Immune checkpoint inhibitors have had a significant impact on the treatment of solid tumors, but there has been limited progress in myeloid malignancies. The low mutational burden of acute myeloid leukemia is a potential reason for the lack of response to T-cell harnessing ICIs. Targeting agents, such as magrolimab and sabatolimab, in combination with other drugs, have shown promising activity in early clinical trials.
Review
Oncology
Alessandro Isidori, Claudio Cerchione, Naval Daver, Courtney DiNardo, Guillermo Garcia-Manero, Marina Konopleva, Elias Jabbour, Farhad Ravandi, Tapan Kadia, Adolfo de la Fuente Burguera, Alessandra Romano, Federica Loscocco, Giuseppe Visani, Giovanni Martinelli, Hagop Kantarjian, Antonio Curti
Summary: Recent advances in understanding the pathogenesis of acute myeloid leukemia (AML) have accelerated the discovery of new drugs and innovative therapeutic approaches, with a particular focus on the role of the immune system in AML development. Efforts in immune therapy have shown promise in improving survival rates for AML patients by targeting leukemia stem cells and utilizing various modalities such as T cell therapy, checkpoint blockade, and leukemia vaccines.
FRONTIERS IN ONCOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Daniela Damiani, Mario Tiribelli
Summary: The prognosis of acute myeloid leukemia (AML) is poor due to tumor cell immune escape, which weakens T-cells. Inhibiting immune checkpoints (ICs) through immune checkpoint inhibitors (ICIs) has emerged as a promising therapeutic strategy for AML. However, the results of clinical trials testing ICIs, alone or in combination with other treatments, in AML are conflicting.
Review
Oncology
Matteo Molica, Salvatore Perrone, Costanza Andriola, Marco Rossi
Summary: Immune-based treatments (ITs) have shown great potential in the treatment of acute myeloid leukemia (AML), but the application of these treatments still faces challenges. This review discusses the important clinical studies of ITs in AML, providing insights into their potential as a promising therapeutic tool for future AML treatment.
Review
Oncology
Matthias Boehme, Sabine Kayser
Summary: This review provides a summary of various immune-based approaches for the treatment of acute myeloid leukemia (AML), including immune checkpoint inhibitors, bispecific T-cell engager antibodies, and chimeric antigen receptor-T-cell (CAR-T) therapies. The development and design of these immune-based strategies have become increasingly important in AML, based on successful immunotherapies in solid cancers. The review covers a wide range of approaches, from antibody drug conjugates to T-cell-based therapies, and discusses ongoing clinical trials and their potential contributions to understanding AML pathogenesis and finding the most effective immunotherapeutic strategies.
Review
Immunology
Johanna Rausch, Evelyn Ullrich, Michael W. M. Kuehn
Summary: AML is a malignant disease that is difficult to treat, especially in patients who cannot undergo intensive chemotherapy. Immunotherapy has been successful in treating solid tumors and lymphatic neoplasms, but its efficacy in AML has been limited. Epigenetic dysregulation is a driver of leukemogenesis, and combining targeted epigenetic drugs with immunotherapy may improve treatment outcomes. Further research is needed to understand the immune functions affected by these drugs and their potential for clinical use.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Oncology
Kousei Nakatsuru, Kazuya Tsubouchi, Minori Hirahata, Tadayuki Nakashima, Yuriko Takahata, Yuki Okamatsu, Yoshimasa Shiraishi, Isamu Okamoto, Taishi Harada
Summary: Therapy-related acute myeloid leukemia (t-AML) and myelodysplastic syndrome (t-MDS) are complications of chemotherapy and/or radiation therapy for malignant diseases. This report describes a case of a patient with advanced lung adenocarcinoma who developed autoimmune hemolytic anemia and MDS associated with a combination of atezolizumab and platinum-based chemotherapy. The patient progressed from t-MDS to t-AML 20 months after treatment initiation, highlighting the increased risk of developing therapy-related myeloid neoplasms with the combination of immune checkpoint inhibitor (ICI) and chemotherapy. Due to the poorer prognosis of t-AML and t-MDS compared to de novo AML and MDS, proper surveillance, follow-up, and treatment are crucial during immunotherapy.
Review
Biotechnology & Applied Microbiology
Luca Guarnera, Carlos Bravo-Perez, Valeria Visconte
Summary: In the past two decades, there has been a significant shift in the treatment and prognosis of acute myeloid leukemia (AML) due to the introduction of new drugs and optimization of therapies. However, the long-term survival of certain subtypes of AML remains low, leading to high expectations for immunotherapies. Despite challenges posed by the characteristics of AML cells, there is ongoing research on potential antigenic targets and future directions for immunotherapies in AML.
BIOENGINEERING-BASEL
(2023)
Review
Pharmacology & Pharmacy
Ying Chen, Jishi Wang, Fengqi Zhang, Ping Liu
Summary: In the past decade, there has been extensive study on the underlying mechanisms of acute myeloid leukemia (AML), increasing our understanding of the disease. However, resistance to chemotherapy and disease relapse remain significant obstacles to successful treatment. Immunotherapies for AML, including immune checkpoint inhibitors and T-cell therapy based on engineered antigen receptor, have recently been developed to tackle these challenges. Our review discusses the recent progress in immunotherapy for AML and identifies the most promising therapies and major challenges.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Quanfeng Zhao, Pan Ma, Peishu Fu, Jiayu Wang, Kejing Wang, Lin Chen, Yang Yang
Summary: This study aimed to evaluate the risk of poly-ADP ribose polymerase (PARP) inhibitors causing myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) based on real-world data. The results showed a significant association between PARP inhibitors and MDS/AML, with a higher risk for MDS than AML. Olaparib had a stronger association with MDS and AML compared to other PARP inhibitors.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Fabio Forghieri, Giovanni Riva, Ivana Lagreca, Patrizia Barozzi, Francesca Bettelli, Ambra Paolini, Vincenzo Nasillo, Beatrice Lusenti, Valeria Pioli, Davide Giusti, Andrea Gilioli, Corrado Colasante, Laura Galassi, Hillary Catellani, Francesca Donatelli, Annalisa Talami, Rossana Maffei, Silvia Martinelli, Leonardo Potenza, Roberto Marasca, Enrico Tagliafico, Rossella Manfredini, Tommaso Trenti, Patrizia Comoli, Mario Luppi
Summary: The C-terminal aminoacidic sequence from NPM1-mutated protein may serve as a leukemia-specific antigen, and different in silico instruments have identified the most immunogenic epitopes. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Simona Pagliuca, Carmelo Gurnari, Keman Zhang, Tariq Kewan, Waled Bahaj, Minako Mori, Ishani Nautiyal, Marie Therese Rubio, Francesca Ferraro, Jaroslaw P. Maciejewski, Li Wang, Valeria Visconte
Summary: V-domain Ig suppressor of T-cell activation (VISTA) is a critical negative regulator of antitumor immune response. In this study, the researchers explored the role of VISTA in the generation of an immune escape environment in acute myeloid leukemia (AML) patients. They found that VISTA expression levels were correlated with AML cell differentiation, NPM1 mutations, and disease recurrence.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Oncology
Xingcheng Yang, Ling Ma, Xiaoying Zhang, Liang Huang, Jia Wei
Summary: Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are clonal hematopoietic stem cell diseases that arise from the bone marrow. Dysregulated immune microenvironment, including the molecules PD-1 and PD-L1, play important roles in the pathogenesis of MDS and AML. However, clinical trials using PD-1/PD-L1 inhibitors have reported mixed responses in patients with these diseases.
EXPERIMENTAL HEMATOLOGY & ONCOLOGY
(2022)
Review
Oncology
Kah Keng Wong, Rosline Hassan, Nik Soriani Yaacob
Summary: Decitabine and guadecitabine are hypomethylating agents that enhance anti-tumor immunity in AML and MDS patients by upregulating cancer/testis antigens, stimulating T cells, and inducing immune checkpoint molecules expression. Combining these agents with cancer vaccines or immune checkpoint blockade therapy shows promising efficacy in treating relapsed/refractory AML and high-risk MDS cases.
FRONTIERS IN ONCOLOGY
(2021)
Review
Chemistry, Medicinal
Laura Jimbu, Oana Mesaros, Cristian Popescu, Alexandra Neaga, Iulia Berceanu, Delia Dima, Mihaela Gaman, Mihnea Zdrenghea
Summary: Checkpoint inhibitors, particularly PD-1/PD-L1 inhibitors, have shown promising results in various solid cancers and hematologic diseases. However, their effectiveness in treating AML is limited, possibly due to disease characteristics and immune system dysregulation, warranting further research for optimal use.
Article
Oncology
Xiaohong Wang, Jonathan E. Schoenhals, Ailin Li, David R. Valdecanas, Huiping Ye, Fenglin Zang, Chad Tang, Ming Tang, Chang-Gong Liu, Xiuping Liu, Sunil Krishnan, James P. Allison, Padmanee Sharma, Patrick Hwu, Ritsuko Komaki, Willem W. Overwijk, Daniel R. Gomez, Joe Y. Chang, Stephen M. Hahn, Maria Angelica Cortez, James W. Welsh
Article
Immunology
Maher G. Nawaf, Maria H. Ulvmar, David R. Withers, Fiona M. McConnell, Fabrina M. Gaspal, Gwilym J. Webb, Nick D. Jones, Hideo Yagita, James P. Allison, Peter J. L. Lane
JOURNAL OF IMMUNOLOGY
(2017)
Article
Oncology
Van K. Morris, Mohamed E. Salem, Halla Nimeiri, Syma Iqbal, Preet Singh, Kristen Ciombor, Blase Polite, Dustin Deming, Emily Chan, James L. Wade, Lianchun Xiao, Tanios Bekaii-Saab, Luis Vence, Jorge Blando, Armeen Mahvash, Wai Chin Foo, Chimela Ohaji, Manolo Pasia, Gail Bland, Aki Ohinata, Jane Rogers, Amir Mehdizadeh, Kimberly Banks, Richard Lanman, Robert A. Wolff, Howard Streicher, James Allison, Padmanee Sharma, Cathy Eng
Article
Biochemistry & Molecular Biology
Jianjun Gao, John F. Ward, Curtis A. Pettaway, Lewis Z. Shi, Sumit K. Subudhi, Luis M. Vence, Hao Zhao, Jianfeng Chen, Hong Chen, Eleni Efstathiou, Patricia Troncoso, James P. Allison, Christopher J. Logothetis, Ignacio I. Wistuba, Manuel A. Sepulveda, Jingjing Sun, Jennifer Wargo, Jorge Blando, Padmanee Sharma
Article
Multidisciplinary Sciences
V. Gopalakrishnan, C. N. Spencer, L. Nezi, A. Reuben, M. C. Andrews, T. V. Karpinets, P. A. Prieto, D. Vicente, K. Hoffman, S. C. Wei, A. P. Cogdill, L. Zhao, C. W. Hudgens, D. S. Hutchinson, T. Manzo, M. Petaccia de Macedo, T. Cotechini, T. Kumar, W. S. Chen, S. M. Reddy, R. Szczepaniak Sloane, J. Galloway-Pena, H. Jiang, P. L. Chen, E. J. Shpall, K. Rezvani, A. M. Alousi, R. F. Chemaly, S. Shelburne, L. M. Vence, P. C. Okhuysen, V. B. Jensen, A. G. Swennes, F. McAllister, E. Marcelo Riquelme Sanchez, Y. Zhang, E. Le Chatelier, L. Zitvogel, N. Pons, J. L. Austin-Breneman, L. E. Haydu, E. M. Burton, J. M. Gardner, E. Sirmans, J. Hu, A. J. Lazar, T. Tsujikawa, A. Diab, H. Tawbi, I. C. Glitza, W. J. Hwu, S. P. Patel, S. E. Woodman, R. N. Amaria, M. A. Davies, J. E. Gershenwald, P. Hwu, J. E. Lee, J. Zhang, L. M. Coussens, Z. A. Cooper, P. A. Futreal, C. R. Daniel, N. J. Ajami, J. F. Petrosino, M. T. Tetzlaff, P. Sharma, J. P. Allison, R. R. Jenq, J. A. Wargo
Article
Cell Biology
Whijae Roh, Pei-Ling Chen, Alexandre Reuben, Christine N. Spencer, Peter A. Prieto, John P. Miller, Vancheswaran Gopalakrishnan, Feng Wang, Zachary A. Cooper, Sangeetha M. Reddy, Curtis Gumbs, Latasha Little, Qing Chang, Wei-Shen Chen, Khalida Wani, Mariana Petaccia De Macedo, Eveline Chen, Jacob L. Austin-Breneman, Hong Jiang, Jason Roszik, Michael T. Tetzlaff, Michael A. Davies, Jeffrey E. Gershenwald, Hussein Tawbi, Alexander J. Lazar, Patrick Hwu, Wen-Jen Hwu, Adi Diab, Isabella C. Glitza, Sapna P. Patel, Scott E. Woodman, Rodabe N. Amaria, Victor G. Prieto, Jianhua Hu, Padmanee Sharma, James P. Allison, Lynda Chin, Jianhua Zhang, Jennifer A. Wargo, P. Andrew Futreal
SCIENCE TRANSLATIONAL MEDICINE
(2017)
Article
Multidisciplinary Sciences
Dmitriy Zamarin, Rikke B. Holmgaard, Jacob Ricca, Tamar Plitt, Peter Palese, Padmanee Sharma, Taha Merghoub, Jedd D. Wolchok, James P. Allison
NATURE COMMUNICATIONS
(2017)
Article
Multidisciplinary Sciences
Julienne L. Carstens, Pedro Correa de Sampaio, Dalu Yang, Souptik Barua, Huamin Wang, Arvind Rao, James P. Allison, Valerie S. LeBleu, Raghu Kalluri
NATURE COMMUNICATIONS
(2017)
Article
Multidisciplinary Sciences
Rina M. Mbofung, Jodi A. McKenzie, Shruti Malu, Min Zhang, Weiyi Peng, Chengwen Liu, Isere Kuiatse, Trang Tieu, Leila Williams, Seram Devi, Emily Ashkin, Chunyu Xu, Lu Huang, Minying Zhang, Amjad H. Talukder, Satyendra C. Tripathi, Hiep Khong, Nikunj Satani, Florian L. Muller, Jason Roszik, Timothy Heffernan, James P. Allison, Gregory Lizee, Sam M. Hanash, David Proia, Rodabe Amaria, R. Eric Davis, Patrick Hwu
NATURE COMMUNICATIONS
(2017)
Article
Oncology
Alexandre Reuben, Rachel Gittelman, Jianjun Gao, Jiexin Zhang, Erik C. Yusko, Chang-Jiun Wu, Ryan Emerson, Jianhua Zhang, Christopher Tipton, Jun Li, Kelly Quek, Vancheswaran Gopalakrishnan, Runzhe Chen, Luis M. Vence, Tina Cascone, Marissa Vignali, Junya Fujimoto, Jaime Rodriguez-Canales, Edwin R. Parra, Latasha D. Little, Curtis Gumbs, Marie-Andree Forget, Lorenzo Federico, Cara Haymaker, Carmen Behrens, Sharon Benzeno, Chantale Bernatchez, Boris Sepesi, Don L. Gibbons, Jennifer A. Wargo, William N. William, Stephen Swisher, John V. Heymach, Harlan Robins, J. Jack Lee, Padmanee Sharma, James P. Allison, P. Andrew Futreal, Ignacio I. Wistuba, Jianjun Zhang
Article
Oncology
Rodabe N. Amaria, Peter A. Prieto, Michael T. Tetzlaff, Alexandre Reuben, Miles C. Andrews, Merrick J. Ross, Isabella C. Glitza, Janice Cormier, Wen-Jen Hwu, Hussein A. Tawbi, Sapna P. Patel, Jeffrey E. Lee, Jeffrey E. Gersbenwaid, Christine N. Spencer, Vancheswaran Gopalakrishnan, Roland Bassett, Lauren Simpson, Rosalind Mouton, Courtney W. Hudgens, Li Zhao, Haifeng Zhu, Zachary A. Cooper, Khalida Wani, Alexander Lazar, Patrick Hwu, Adi Diab, Michael K. Wong, Jennifer L. McQuade, Richard Royal, Anthony Lucci, Elizabeth M. Burton, Sangeetha Reddy, Padmanee Sharma, James Allison, Phillip A. Futreal, Scott E. Woodman, Michael A. Davies, Jennifer A. Wargo
Review
Oncology
Naval Daver, Prajwal Boddu, Guillermo Garcia-Manero, Shalini Singh Yadav, Padmanee Sharman, James Allison, Hagop Kantarjian
Article
Oncology
Charlotte E. Ariyan, Mary Sue Brady, Robert H. Siegelbaum, Jian Hu, Danielle M. Bello, Jamie Rand, Charles Fisher, Robert A. Lefkowitz, Kathleen S. Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y. Rudensky, Jedd D. Wolchok, James P. Allison
CANCER IMMUNOLOGY RESEARCH
(2018)
Article
Biochemistry & Molecular Biology
Spencer C. Wei, Jacob H. Levine, Alexandria P. Cogdill, Yang Zhao, Nana-Ama A. S. Anang, Miles C. Andrews, Padmanee Sharma, Jing Wang, Jennifer A. Wargo, Dana Pe'er, James P. Allison