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Pioneering research and recent advances in Immune Checkpoint Therapy

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Immunotherapy is undoubtedly one of the most exciting discoveries of the 21st century. In October 2018, the Nobel prize committee duly recognized two scientists, Dr. James Allison and Dr. Tasuku Honjo for their pioneering research in immune checkpoint therapy, an approach that involves harnessing one's own immune cells to attack tumor cells. Although this is a significant step forward in cancer treatment, we are still far from a cancer free future. 

This special collection on immune checkpoint therapy is a compilation of seminal articles that would serve as a useful reference to scientists working in this evolving area of research. In addition to articles published by Nobel prize winners Dr. James Allison and Dr. Tasuku Honjo, widely read articles contributed by other scientists have also been included. We are proud to honor the work of all our authors and join them in their mission to make strides in cancer treatment.

  1. Content type: Review

    Hepatocellular carcinoma (HCC) is one of the most common tumors in the world, and its mortality is still on the rise. Limited treatments and low chemotherapy sensitivity of HCC make new therapeutic strategies ...

    Authors: Feifei Liu, Yanning Liu and Zhi Chen

    Citation: Journal of Hematology & Oncology 2018 11:126

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  2. Content type: Review

    The immune system is composed of immune as well as non-immune cells. As this system is a well-established component of human papillomavirus- (HPV)-related carcinogenesis, high risk human papillomavirus (hrHPV)...

    Authors: Marconi Rego Barros Jr, Cristiane Moutinho Lagos de Melo, Maria Luiza Carneiro Moura Gonçalves Rego Barros, Rita de Cássia Pereira de Lima, Antonio Carlos de Freitas and Aldo Venuti

    Citation: Journal of Experimental & Clinical Cancer Research 2018 37:137

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  3. Content type: Review

    Immune checkpoints include stimulatory and inhibitory checkpoint molecules. In recent years, inhibitory checkpoints, including cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), programmed cell death protei...

    Authors: Feng Xu, Tianqiang Jin, Yuwen Zhu and Chaoliu Dai

    Citation: Journal of Experimental & Clinical Cancer Research 2018 37:110

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  4. Content type: Case report

    Metastatic melanoma is an aggressive skin cancer with a poor prognosis. Current treatment strategies for high-stage melanoma are based around the use of immunotherapy with immune checkpoint inhibitors such as ...

    Authors: Carmela De Santo, Paul Cheng, Andrew Beggs, Sharon Egan, Alberto Bessudo and Francis Mussai

    Citation: Journal of Hematology & Oncology 2018 11:68

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  5. Content type: Case report

    Nivolumab is an immune checkpoint inhibitor targeting programmed death-1 protein and has been approved for the treatment of multiple advanced malignancies. Adverse effects of immune checkpoint inhibitors are d...

    Authors: Shagufta Shaheen, Hamid Mirshahidi, Gayathri Nagaraj and Chung-Tsen Hsueh

    Citation: Experimental Hematology & Oncology 2018 7:11

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  6. Content type: Research

    While conventional chemotherapy is effective at eliminating the bulk of leukemic cells, chemotherapy resistance in acute myeloid leukemia (AML) is a prevalent problem that hinders conventional therapies and co...

    Authors: Branson Chen, Jong Bok Lee, Hyeonjeong Kang, Mark D. Minden and Li Zhang

    Citation: Journal of Experimental & Clinical Cancer Research 2018 37:88

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  7. Content type: Review

    In the advent of Immune Checkpoint inhibitors (ICI) and of CAR-T adoptive T-cells, the new frontier in Oncology is Cancer Immunotherapy because of its ability to provide long term clinical benefit in metastati...

    Authors: Luigi Aurisicchio, Matteo Pallocca, Gennaro Ciliberto and Fabio Palombo

    Citation: Journal of Experimental & Clinical Cancer Research 2018 37:86

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  8. Content type: Review

    Immune checkpoint inhibitors (ICIs) therapy is a novel strategy for cancer treatments in recent years. However, it was observed that most patients treated with ICIs could not get benefit from the therapy, whic...

    Authors: Ming Yi, Shengnan Yu, Shuang Qin, Qian Liu, Hanxiao Xu, Weiheng Zhao, Qian Chu and Kongming Wu

    Citation: Journal of Hematology & Oncology 2018 11:47

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  9. Content type: Case report

    Immune checkpoint blockade (ICB) is becoming an increasingly prevalent strategy in the clinical realm of cancer therapeutics. With more patients being administered ICB for a host of tumor types, the scope of a...

    Authors: D. E. Meyers, W. F. Hill, A. Suo, V. Jimenez-Zepeda, T. Cheng and N. A. Nixon

    Citation: Experimental Hematology & Oncology 2018 7:6

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  10. Content type: Review

    Immune checkpoints consist of inhibitory and stimulatory pathways that maintain self-tolerance and assist with immune response. In cancer, immune checkpoint pathways are often activated to inhibit the nascent ...

    Authors: Julian A. Marin-Acevedo, Bhagirathbhai Dholaria, Aixa E. Soyano, Keith L. Knutson, Saranya Chumsri and Yanyan Lou

    Citation: Journal of Hematology & Oncology 2018 11:39

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  11. Content type: Research article

    While immune checkpoint blockade has greatly improved clinical outcomes in diseases such as melanoma, there remains a need for predictive biomarkers to determine who will likely benefit most from which therapy...

    Authors: Priyanka B. Subrahmanyam, Zhiwan Dong, Daniel Gusenleitner, Anita Giobbie-Hurder, Mariano Severgnini, Jun Zhou, Michael Manos, Lauren M. Eastman, Holden T. Maecker and F. Stephen Hodi

    Citation: Journal for ImmunoTherapy of Cancer 2018 6:18

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  12. Content type: Research

    T-cell immunoglobulin mucin 3 (TIM3) is a negative immune checkpoint and plays a crucial part in tumor-induced immune suppression. However, the mechanism of TIM3 in regulating immunosuppression in head and nec...

    Authors: Jian-Feng Liu, Lei Wu, Lei-Lei Yang, Wei-Wei Deng, Liang Mao, Hao Wu, Wen-Feng Zhang and Zhi-Jun Sun

    Citation: Journal of Experimental & Clinical Cancer Research 2018 37:44

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  13. Content type: Review

    The programmed death receptor 1 (PD-1) protein is a cell-surface receptor on certain lymphocytes that, with its ligand programmed death ligand 1 (PD-L1), helps to down-regulate immune responses. Many cancer ty...

    Authors: Margarita Udall, Maria Rizzo, Juliet Kenny, Jim Doherty, SueAnn Dahm, Paul Robbins and Eric Faulkner

    Citation: Diagnostic Pathology 2018 13:12

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  14. Content type: Research

    Immune checkpoint inhibitors have led to a breakthrough in solid tumor immunotherapy, but related studies on musculoskeletal tumors are few, especially for PD-L2.

    Authors: Bingxin Zheng, Tingting Ren, Yi Huang, Kunkun Sun, Shidong Wang, Xing Bao, Kuisheng Liu and Wei Guo

    Citation: Journal of Hematology & Oncology 2018 11:16

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    The Correction to this article has been published in Journal of Hematology & Oncology 2018 11:37

  15. Content type: Rapid communication

    Natural killer/T-cell lymphoma (NKTCL) is a rare subtype of non-Hodgkin lymphoma that is associated with a poor outcome. Currently, the treatment needs of NKTCL remain unmet, and efforts to further improve tre...

    Authors: Xin Li, Yasong Cheng, Mingzhi Zhang, Jiaqin Yan, Ling Li, Xiaorui Fu, Xudong Zhang, Yu Chang, Zhenchang Sun, Hui Yu, Lei Zhang, Xinhua Wang, Jingjing Wu, Zhaoming Li, Feifei Nan, Li Tian…

    Citation: Journal of Hematology & Oncology 2018 11:15

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  16. Content type: Review

    Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1...

    Authors: Jun Gong, Alexander Chehrazi-Raffle, Srikanth Reddi and Ravi Salgia

    Citation: Journal for ImmunoTherapy of Cancer 2018 6:8

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  17. Content type: Research

    Surgical resection combined with adjuvant chemotherapy is considered as the gold-standard treatment for advanced colorectal cancer patients. These patients have a poor 5-year survival rate of 5% or less. Furth...

    Authors: Yunqing Xie, Lijie Huang, Luchuan Chen, Xiaowei Lin, Li Chen and Qiuhong Zheng

    Citation: World Journal of Surgical Oncology 2017 15:209

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  18. Content type: Position article and guidelines

    Cancer immunotherapy has transformed the treatment of cancer. However, increasing use of immune-based therapies, including the widely used class of agents known as immune checkpoint inhibitors, has exposed a d...

    Authors: I. Puzanov, A. Diab, K. Abdallah, C. O. Bingham III, C. Brogdon, R. Dadu, L. Hamad, S. Kim, M. E. Lacouture, N. R. LeBoeuf, D. Lenihan, C. Onofrei, V. Shannon, R. Sharma, A. W. Silk, D. Skondra…

    Citation: Journal for ImmunoTherapy of Cancer 2017 5:95

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  19. Content type: Research

    Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment how...

    Authors: Su Yin Lim, Jenny H. Lee, Sarah J. Welsh, Seong Beom Ahn, Edmond Breen, Alamgir Khan, Matteo S. Carlino, Alexander M. Menzies, Richard F. Kefford, Richard A. Scolyer, Georgina V. Long and Helen Rizos

    Citation: Biomarker Research 2017 5:32

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  20. Content type: Case report

    The treatment algorithm for metastatic non-small cell lung cancers (NSCLCs) has been evolving rapidly due to the development of new therapeutic agents. Although guidelines are provided by National Comprehensiv...

    Authors: Shuyu D. Li, Annia Martial, Alexa B. Schrock and Jane J. Liu

    Citation: Experimental Hematology & Oncology 2017 6:29

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  21. Content type: Research

    Recently, immunotherapy with anti-PD-1 antibodies has shown clinical benefit in recurrent Small Cell Lung Cancer (SCLC). Since anti-PD-1 re-activates anti-tumor Cytotoxic T Lymphocyte (CTL) responses, it is cr...

    Authors: Grazia Carbotti, Amin Reza Nikpoor, Paola Vacca, Rosaria Gangemi, Chiara Giordano, Francesco Campelli, Silvano Ferrini and Marina Fabbi

    Citation: Journal of Experimental & Clinical Cancer Research 2017 36:140

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  22. Content type: Research

    The purpose of this study was to elucidate the regulation of programmed death ligand 1 (PDL1), lactate dehydrogenase A (LDHA) and miR-34a in triple negative breast cancer (TNBC) and to explore the function and...

    Authors: Xiaojia Huang, Xinhua Xie, Hua Wang, Xiangsheng Xiao, Lu Yang, Zhi Tian, Xiaofang Guo, Lijuan Zhang, Hailin Tang and Xiaoming Xie

    Citation: Journal of Experimental & Clinical Cancer Research 2017 36:129

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  23. Content type: Review

    Treatment modalities of head and neck squamous cell cancer include surgery, radiation, chemotherapy, targeted agents and immune checkpoint inhibition. Treatment is often toxic and can affect long-term function...

    Authors: Nnamdi Eze, Ying-Chun Lo and Barbara Burtness

    Citation: Cancers of the Head & Neck 2017 2:6

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  24. Content type: Review

    Gastrointestinal (GI) malignancies are the most prevalent tumors worldwide, with increasing incidence and mortality. Although surgical resection, chemotherapy, radiotherapy, and molecular targeted therapy have...

    Authors: Junyu Long, Jianzhen Lin, Anqiang Wang, Liangcai Wu, Yongchang Zheng, Xiaobo Yang, Xueshuai Wan, Haifeng Xu, Shuguang Chen and Haitao Zhao

    Citation: Journal of Hematology & Oncology 2017 10:146

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  25. Content type: Review

    Adaptive immunity is critical for disease progression and modulates T cell (TC) and antigen-presenting cell (APC) functions. Three signals were initially proposed for adaptive immune activation: signal 1 antig...

    Authors: Jin Dai, Pu Fang, Jason Saredy, Hang Xi, Cueto Ramon, William Yang, Eric T. Choi, Yong Ji, Wei Mao, Xiaofeng Yang and Hong Wang

    Citation: Journal of Hematology & Oncology 2017 10:141

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  26. Content type: Review

    Programmed death ligand 1 (PD-L1) has emerged as a biomarker that can help to predict responses to immunotherapies targeted against PD-L1 and its receptor (PD-1). Companion tests for evaluating PD-L1 expressio...

    Authors: Delong Liu, Shuhang Wang and Wendy Bindeman

    Citation: Journal of Hematology & Oncology 2017 10:110

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  27. Content type: Review

    Inhibitory molecules such as PD-1, CTLA-4, LAG-3, or TIM-3 play a role to keep a balance in immune function. However, many cancers exploit such molecules to escape immune surveillance. Accumulating data suppor...

    Authors: Chi Young Ok and Ken H. Young

    Citation: Journal of Hematology & Oncology 2017 10:103

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  28. Content type: Review

    Patients with advanced melanoma have a compromised anti-tumor immune response leading to tumor immune tolerance and a tumor microenvironment conducive to disease progression. Immunotherapy that successfully ov...

    Authors: Tala Achkar and Ahmad A. Tarhini

    Citation: Journal of Hematology & Oncology 2017 10:88

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  29. Content type: Review

    Immunotherapy has recently emerged as the fourth pillar of cancer treatment, joining surgery, radiation, and chemotherapy. While early immunotherapies focused on accelerating T-cell activity, current immune-ch...

    Authors: Yoshiko Iwai, Junzo Hamanishi, Kenji Chamoto and Tasuku Honjo

    Citation: Journal of Biomedical Science 2017 24:26

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  30. Content type: Review

    Locally advanced (stage III or IV) squamous cell carcinoma of the head and neck (SCCHN) often requires multimodal treatment, consisting of a combination of surgery, radiation, and/or systemic therapy, namely c...

    Authors: Paolo Bossi and Francesca Platini

    Citation: Cancers of the Head & Neck 2017 2:2

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  31. Content type: Review

    Cluster of differentiation 47 (CD47) (also known as integrin-associated protein) is a ubiquitously expressed glycoprotein of the immunoglobulin superfamily that plays a critical role in self-recognition. Vario...

    Authors: Xiaojuan Liu, Hyunwoo Kwon, Zihai Li and Yang-xin Fu

    Citation: Journal of Hematology & Oncology 2017 10:12

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  32. Content type: Case Report

    Understanding the role of alternative complement pathway dysregulation in membranoproliferative glomerulonephritis (MPGN) has led to a dramatic shift in its classification into two subgroups: immune complex-me...

    Authors: Tanja Kersnik Levart, Dušan Ferluga, Alenka Vizjak, Jerica Mraz and Nika Kojc

    Citation: Diagnostic Pathology 2016 11:94

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  33. Content type: Case report

    Novel immunotherapies, or checkpoint inhibitors, targeting programmed cell death protein-1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) have significantly improved outcomes for patients with...

    Authors: Marc Uemura, Van A. Trinh, Cara Haymaker, Natalie Jackson, Dae Won Kim, James P. Allison, Padmanee Sharma, Luis Vence, Chantale Bernatchez, Patrick Hwu and Adi Diab

    Citation: Journal of Hematology & Oncology 2016 9:81

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  34. Content type: Review

    With the rapid succession of new effective agents for melanoma in the recent years, the paradigm for treatment of metastatic melanoma is changing. The success of combining multiple effective agents compared wi...

    Authors: Eddy C. Hsueh and Kalyan C. Gorantla

    Citation: Experimental Hematology & Oncology 2016 5:23

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  35. Content type: Research

    PD-L1 is a glycoprotein from the family of T-cell co-stimulatory molecules that are constitutively expressed by macrophages. Aberrant expression of PD-L1 is observed in human cancers associated with inhibition...

    Authors: Katia R M Leite, Sabrina T. Reis, José Pontes Junior, Marcelo Zerati, Daniel de Oliveira Gomes, Luiz H. Camara-Lopes and Miguel Srougi

    Citation: Diagnostic Pathology 2015 10:189

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  36. Content type: Case Report

    Medullary carcinoma is a rare type of colon cancer with characteristic clinical and molecular features. Notably, despite its high-grade histology, the prognosis is generally better than for colonic adenocarcin...

    Authors: Andrew Mitchell and Yves Bendavid

    Citation: Diagnostic Pathology 2014 9:204

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  37. Content type: Research

    Soft tissue sarcomas (STS) are rare. We evaluated the WT1 protein expression level in various types of STS and elucidated the value of WT1 as a prognostic factor and a possible therapeutic target.

    Authors: Ahrong Kim, Eun Young Park, Kyungbin Kim, Jeong Hee Lee, Dong Hoon Shin, Jee Yeon Kim, Do Youn Park, Chang Hun Lee, Mee Young Sol, Kyung Un Choi, Jeung Il Kim and In Sook Lee

    Citation: World Journal of Surgical Oncology 2014 12:214

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  38. Content type: Review

    Prediction of clinical outcome in cancer is usually achieved by histopathological evaluation of tissue samples obtained during surgical resection of the primary tumor. Traditional tumor staging (AJCC/UICC-TNM ...

    Authors: Jérôme Galon, Franck Pagès, Francesco M Marincola, Helen K Angell, Magdalena Thurin, Alessandro Lugli, Inti Zlobec, Anne Berger, Carlo Bifulco, Gerardo Botti, Fabiana Tatangelo, Cedrik M Britten, Sebastian Kreiter, Lotfi Chouchane, Paolo Delrio, Hartmann Arndt…

    Citation: Journal of Translational Medicine 2012 10:205

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  39. Content type: Commentary

    Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a ...

    Authors: Bernard A Fox, Dolores J Schendel, Lisa H Butterfield, Steinar Aamdal, James P Allison, Paolo Antonio Ascierto, Michael B Atkins, Jirina Bartunkova, Lothar Bergmann, Neil Berinstein, Cristina C Bonorino, Ernest Borden, Jonathan L Bramson, Cedrik M Britten, Xuetao Cao, William E Carson…

    Citation: Journal of Translational Medicine 2011 9:214

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