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Advances in Cancer Immunotherapy

Cancer ImmunotherapyGuest Edited by: Prof. Mauro Castelli1, Prof. Gabriella D’Orazi2 & Dr. Anand Rotte3 

1 - Editor-in-Chief of Journal of Experimental & Clinical Cancer Research
2 - Department of Medical Sciences, University “G. D’Annunzio”, Chieti, Italy
3 - Clinical & Regulatory Affairs, NevroCorp, Redwood City, CA, USA


Drugs acting by stimulating the immune responses have been immensely successful in the treatment of cancer. Several classes of immunotherapeutics including cytokines such as interleukin-2 (IL-2) and interferon-α2b (IFN-α2b), monoclonal antibodies against immune checkpoints, autologous dendritic cells expressing tumor antigen, genetically engineered oncolytic viruses, and T-cells engineered to expressed chimeric antigen receptors (CAR-T cells), have been approved for multiple cancer subtypes, including both solid tumors, as well as hematological cancers. Durable response rates are considered as the greatest advantages of immunotherapy but its success is overshadowed by low response rates. Insufficient immune activation and involvement of multiple immunosuppressive pathways are thought to be the reasons for treatment failure in non-responding patients. To increase the response rates, a combination of immunotherapeutics has been suggested. Research is ongoing to design better and safer combinations by altering dosage or sequence of administration of approved drugs, or by developing new drugs and their combinations.

The purpose of this thematic series, published in Journal of Experimental & Clinical Cancer Research, is to summarize some of the highlights of cancer immunotherapy that may provide new opportunities for personalized anti-cancer therapy as well as presenting challenges on the road to the clinic. 

Submission to this series is now closed.

  1. We investigated the role of PD-L1 in the metabolic reprogramming of non-small cell lung cancer (NSCLC).

    Authors: Sehui Kim, Ji-Young Jang, Jaemoon Koh, Dohee Kwon, Young A. Kim, Jin Chul Paeng, Chan-Young Ock, Bhumsuk Keam, Miso Kim, Tae Min Kim, Dae Seog Heo, Doo Hyun Chung and Yoon Kyung Jeon

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:462

    Content type: Research

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  2. Inefficient T-cell access to the tumor microenvironment (TME) is among the causes of tumor immune-resistance. Previous evidence demonstrated that targeting CXCR4 improves anti-PD-1/PD-L1 efficacy reshaping TME...

    Authors: Crescenzo D’Alterio, Maria Buoncervello, Caterina Ieranò, Maria Napolitano, Luigi Portella, Giuseppina Rea, Antonio Barbieri, Antonio Luciano, Giosuè Scognamiglio, Fabiana Tatangelo, Anna Maria Anniciello, Mario Monaco, Ernesta Cavalcanti, Piera Maiolino, Giulia Romagnoli, Claudio Arra…

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:432

    Content type: Research

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  3. Until very few years ago, the oncology community dogmatically excluded any clinical potential for immunotherapy in controlling brain metastases. Therefore, despite the significant therapeutic efficacy of monoc...

    Authors: Anna Maria Di Giacomo, Monica Valente, Alfonso Cerase, Maria Fortunata Lofiego, Francesca Piazzini, Luana Calabrò, Elisabetta Gambale, Alessia Covre and Michele Maio

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:419

    Content type: Review

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  4. Long non-coding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP), has been demonstrated to be a vital biomarker when evaluating the prognosis of multiple cancers. Nevertheless, the potential function of...

    Authors: Anquan Shang, Weiwei Wang, Chenzheng Gu, Chen Chen, Bingjie Zeng, Yibao Yang, Ping Ji, Junjun Sun, Junlu Wu, Wenying Lu, Zujun Sun and Dong Li

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:411

    Content type: Research

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  5. Immune checkpoint inhibition and in particular anti-PD-1 immunotherapy have revolutionized the treatment of advanced melanoma. In this regard, higher tumoral PD-L1 protein (gene name: CD274) expression is associa...

    Authors: Alexander Thiem, Sonja Hesbacher, Hermann Kneitz, Teresa di Primio, Markus V. Heppt, Heike M. Hermanns, Matthias Goebeler, Svenja Meierjohann, Roland Houben and David Schrama

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:397

    Content type: Research

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  6. Hepatocellular carcinoma (HCC) ranks the most common primary liver malignancy and the third leading cause of tumor-related mortality worldwide. Unfortunately, despite advances in HCC treatment, less than 40% o...

    Authors: Yaojie Fu, Shanshan Liu, Shan Zeng and Hong Shen

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:396

    Content type: Review

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  7. Immunotherapeutic approaches designed to augment T and B cell mediated killing of tumor cells has met with clinical success in recent years suggesting tremendous potential for treatment in a broad spectrum of ...

    Authors: Lawrence H. Cheung, Yunli Zhao, Ana Alvarez-Cienfuegos, Khalid A. Mohamedali, Yu J. Cao, Walter N. Hittelman and Michael G. Rosenblum

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:332

    Content type: Research

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  8. Programmed death 1 (PD-1) blockade has great effect in the prevention of oral precancerous lesions, but the drug resistance has also been observed. The determinants of immune resistance during the malignant tr...

    Authors: Liling Wen, Huanzi Lu, Qiusheng Li, Qunxing Li, Shuqiong Wen, Dikan Wang, Xi Wang, Juan Fang, Jun Cui, Bin Cheng and Zhi Wang

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:299

    Content type: Research

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  9. Glioma is one of the most aggressive malignant brain tumors which is characterized with highly infiltrative growth and poor prognosis. NKAP (NF-κB activating protein) is a widely expressed 415-amino acid nucle...

    Authors: Guangyan Gu, Taihong Gao, Lu Zhang, Xiuyang Chen, Qi Pang, Yanan Wang, Dan Wang, Jie Li and Qian Liu

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:291

    Content type: Research

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  10. Immunotherapy has become an established pillar of cancer treatment improving the prognosis of many patients with a broad variety of hematological and solid malignancies. The two main drivers behind this succes...

    Authors: Stephan Kruger, Matthias Ilmer, Sebastian Kobold, Bruno L. Cadilha, Stefan Endres, Steffen Ormanns, Gesa Schuebbe, Bernhard W. Renz, Jan G. D’Haese, Hans Schloesser, Volker Heinemann, Marion Subklewe, Stefan Boeck, Jens Werner and Michael von Bergwelt-Baildon

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:268

    Content type: Review

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  11. Anti-PD-1/PD-L1 drugs are effective as monotherapy in a proportion of NSCLC patients and there is a strong rationale for combining them with targeted therapy. Inhibition of MAPK pathway may have pleiotropic ef...

    Authors: Carminia Maria Della Corte, Giusi Barra, Vincenza Ciaramella, Raimondo Di Liello, Giovanni Vicidomini, Silvia Zappavigna, Amalia Luce, Marianna Abate, Alfonso Fiorelli, Michele Caraglia, Mario Santini, Erika Martinelli, Teresa Troiani, Fortunato Ciardiello and Floriana Morgillo

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:253

    Content type: Research

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  12. The study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells.

    Authors: Chuanbao Cui, Kaiwen Fu, Lu Yang, Shuzhi Wu, Zuojie Cen, Xingxing Meng, Qiongguang Huang and Zhichun Xie

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:229

    Content type: Research

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  13. Several targeted immunotherapies have recently showed significant advances in treatment of non-small cell lung cancer (NSCLC), including antibodies and inhibitors targeting programmed death-1 (PD-1) and its li...

    Authors: Yanhui Chen, Quanxing Liu, Zhiming Chen, Yating Wang, Wanning Yang, Ying Hu, Wenbo Han, Hui Zeng, Haitao Ma, Jigang Dai and Henghui Zhang

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:193

    Content type: Research

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  14. Modulation of cell surface expression of MHC class I chain-related protein A/B (MICA/B) has been proven to be one of the mechanisms by which tumor cells escape from NK cell-mediated killing. Abnormal metabolic...

    Authors: Qingke Duan, Hehe Li, Chenggang Gao, Hengqiang Zhao, Shihong Wu, Heshui Wu, Chunyou Wang, Qiang Shen and Tao Yin

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:192

    Content type: Research

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  15. Chimeric antigen receptor (CAR)-engineered T cells have displayed outstanding performance in the treatment of patients with hematological malignancies. However, their efficacy against solid tumors has been lar...

    Authors: Yitian Wang, Wei Yu, Jian Zhu, Junjie Wang, Kaishun Xia, Chengzhen Liang and Huimin Tao

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:168

    Content type: Research

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  16. Pancreatic cancer is one of the most lethal type of cancers, with an overall five-year survival rate of less than 5%. It is usually diagnosed at an advanced stage with limited therapeutic options. To date, no ...

    Authors: Chin-King Looi, Felicia Fei-Lei Chung, Chee-Onn Leong, Shew-Fung Wong, Rozita Rosli and Chun-Wai Mai

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:162

    Content type: Review

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  17. The recent developments in immuno-oncology have opened an unprecedented avenue for the emergence of vaccine strategies. Therapeutic DNA cancer vaccines are now considered a very promising strategy to activate ...

    Authors: Alessandra Lopes, Gaëlle Vandermeulen and Véronique Préat

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:146

    Content type: Review

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  18. Autophagy, a process for degrading intracellular substances to maintain basal metabolic turnover, is known to be perturbed in gastric cancer. Programmed cell death-1 (PD-1) with its ligand (PD-L1) are importan...

    Authors: Xiaojuan Wang, William K. K. Wu, Jing Gao, Zhongwu Li, Bin Dong, Xiaoting Lin, Yilin Li, Yanyan Li, Jifang Gong, Changsong Qi, Zhi Peng, Jun Yu and Lin Shen

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:140

    Content type: Research

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  19. Immune checkpoint inhibitor therapy has changed clinical practice for patients with different cancers, since these agents have demonstrated a significant improvement of overall survival and are effective in ma...

    Authors: Francesca Di Modugno, Cristina Colosi, Paola Trono, Giuseppe Antonacci, Giancarlo Ruocco and Paola Nisticò

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:117

    Content type: Review

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  20. Though immune checkpoint blockade (ICB) against PD-1 has shown success in the treatment of lung cancer, not all patients respond. We have previously shown that adoptive transfer of double negative T (DNT) cell...

    Authors: Linan Fang, Dalam Ly, Si-si Wang, Jong Bok Lee, Hyeonjeong Kang, Hao Xu, Junlin Yao, Ming-sound Tsao, Wei Liu and Li Zhang

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:123

    Content type: Research

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  21. Novel therapeutic strategies are urgently needed for the treatment of metastatic Urothelial Bladder Cancer. DNA damaging repair (DDR) targeting has been introduced in cinical trials for bladder cancer patients...

    Authors: Daniela Criscuolo, Francesco Morra, Riccardo Giannella, Roberta Visconti, Aniello Cerrato and Angela Celetti

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:91

    Content type: Review

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  22. The muscle invasive form of urothelial bladder cancer (UBC) is a deadly disease. Currently, the therapeutic approach of UBC is mostly based on surgery and standard chemotherapy.

    Authors: Francesco Morra, Francesco Merolla, Daniela Criscuolo, Luigi Insabato, Riccardo Giannella, Gennaro Ilardi, Aniello Cerrato, Roberta Visconti, Stefania Staibano and Angela Celetti

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:90

    Content type: Research

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  23. PD-1/PD-L1 checkpoint blockades have achieved significant progress in several kinds of tumours. Pembrolizumab, which targets PD-1, has been approved as a first-line treatment for advanced non-small cell lung c...

    Authors: Xin Wang, Gaochao Guo, Hui Guan, Yang Yu, Jie Lu and Jinming Yu

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:87

    Content type: Review

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  24. Despite the increasing progress in targeted and immune based-directed therapies for other solid organ malignancies, currently there is no targeted therapy available for TNBCs. A number of mechanisms have been ...

    Authors: Murugan Kalimutho, Debottam Sinha, Deepak Mittal, Sriganesh Srihari, Devathri Nanayakkara, Shagufta Shafique, Prahlad Raninga, Purba Nag, Kate Parsons and Kum Kum Khanna

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:85

    Content type: Research

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  25. Personalized cancer vaccines based on neoantigens have reached the clinical trial stage in melanoma. Different vaccination protocols showed efficacy in preclinical models without a clear indication of the qual...

    Authors: Luigi Aurisicchio, Erika Salvatori, Lucia Lione, Silvio Bandini, Matteo Pallocca, Roberta Maggio, Maurizio Fanciulli, Francesca De Nicola, Frauke Goeman, Gennaro Ciliberto, Antonella Conforti, Laura Luberto and Fabio Palombo

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:78

    Content type: Research

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  26. Pancreatic ductal adenocarcinoma is one of the leading causes of cancer-related death worldwide. Immune checkpoint blockade therapy, including anti-PD-1 and anti-PD-L1, is a new therapeutic strategy for cancer...

    Authors: Ping Fan, Jingyuan Zhao, Zibo Meng, Heyu Wu, Bo Wang, Heshui Wu and Xin Jin

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:47

    Content type: Research

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  27. Human microsatellite-stable (MSS) colorectal cancers (CRCs) are immunologically “cold” tumour subtypes characterized by reduced immune cytotoxicity. The molecular linkages between immune-resistance and human M...

    Authors: Guido Giordano, Pietro Parcesepe, Mario Rosario D’Andrea, Luigi Coppola, Tania Di Raimo, Andrea Remo, Erminia Manfrin, Claudia Fiorini, Aldo Scarpa, Carla Azzurra Amoreo, Fabiana Conciatori, Michele Milella, Francesca Pia Caruso, Luigi Cerulo, Almudena Porras and Massimo Pancione

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:28

    Content type: Research

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  28. Triple negative breast cancer (TNBC) is an aggressive malignancy with poor prognosis, in part because of the current lack of any approved molecularly targeted therapy. We evaluated various combinations of thre...

    Authors: Elaine Reguera-Nuñez, Ping Xu, Annabelle Chow, Shan Man, Frank Hilberg and Robert S. Kerbel

    Citation: Journal of Experimental & Clinical Cancer Research 2019 38:16

    Content type: Research

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  29. Abundant evidence shows that triple-negative breast cancer (TNBC) is heterogeneous, and many efforts have been devoted to identifying TNBC subtypes on the basis of genomic profiling. However, few studies have ...

    Authors: Yin He, Zehang Jiang, Cai Chen and Xiaosheng Wang

    Citation: Journal of Experimental & Clinical Cancer Research 2018 37:327

    Content type: Research

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  30. This commentary wishes to highlight the 2018 Nobel Prize in Medicine awarded to two cancer immunotherapy scientists, Prof James Allison and Prof Tasuku Honjo, for their discovery on unleashing the body’s immun...

    Authors: Anand Rotte, Gabriella D’Orazi and Madhuri Bhandaru

    Citation: Journal of Experimental & Clinical Cancer Research 2018 37:262

    Content type: Commentary

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