Commentary/Editorials

Immune induction strategies to enhance responses to PD-1 blockade: lessons from the TONIC trial

Programmed cell death protein 1 (PD-1) blockade is only effective in a minority of patients, prompting the search for combinatorial therapies that increase responses. Identifying effective combinations require...

Authors: Sandra Demaria, Emanuela Romano, Muriel Brackstone and Silvia C. Formenti

Anti-TNF, a magic bullet in cancer immunotherapy?

Immune checkpoint blockers (ICB) have revolutionized cancer therapy. However, complete response is observed in a minority of patients and most patients develop immune-related adverse events (irAEs). These incl...

Authors: Anne Montfort, Carine Dufau, Céline Colacios, Nathalie Andrieu-Abadie, Thierry Levade, Thomas Filleron, Jean-Pierre Delord, Maha Ayyoub, Nicolas Meyer and Bruno Ségui

Moving forward to address key unanswered questions on targeting PD-1/PD-L1 in cancer: limitations in preclinical models and the need to incorporate human modifying factors

The tremendous clinical success of immune checkpoint inhibition (ICI), particularly targeting the programmed cell death protein 1 (PD-1)/programmed death-ligand 1/2 (PD-L1/2) pathway, has resulted in applicati...

Authors: Catherine T. Le and William J. Murphy

Antibiotic therapy and outcome from immune-checkpoint inhibitors

Sensitivity to immune checkpoint inhibitor (ICPI) therapy is governed by a complex interplay of tumor and host-related determinants. Epidemiological studies have highlighted that exposure to antibiotic therapy...

Authors: David J. Pinato, Daria Gramenitskaya, Daniel M. Altmann, Rosemary J. Boyton, Benjamin H. Mullish, Julian R. Marchesi and Mark Bower

Challenges in assessing the clinical utility and economic value of immune checkpoint inhibitor therapies of Cancer

Advances in the immunotherapy of cancer have prolonged survival for cancer patients, but the clinical and financial impact of treatments must be considered in determining the overall clinical utility and econo...

Authors: Peter Paul Yu, Omar Eton and Louis P. Garrison

Designing gene panels for tumor mutational burden estimation: the need to shift from ‘correlation’ to ‘accuracy’

Tumor mutational burden (TMB) assessment is at the forefront in precision medicine. The TMB could represent a biomarker for immune checkpoint inhibitors (ICIs) responses. Whole exome sequencing (WES) is the go...

Authors: Hao-Xiang Wu, Zi-Xian Wang, Qi Zhao, Feng Wang and Rui-Hua Xu

Hypothesis: does adrenalitis caused by immune checkpoint-inhibitors put melanoma patients at an elevated risk for recurrence?

Primary adrenal failure (Addison’s disease) is a rare complication of immune checkpoint inhibitor (ICI) therapy. Untreated – and also sometimes under adequate hydrocortisone replacement therapy – the levels of...

Authors: Igor Alexander Harsch

Comparative safety and efficacy of anti-PD-1 monotherapy, chemotherapy alone, and their combination therapy in advanced nasopharyngeal carcinoma: findings from recent advances in landmark trials

Recent phase 1–2 trials reported manageable safety profiles and promising antitumor activities of anti-PD-1 drugs (pembrolizumab, nivolumab, camrelizumab and JS001) with/without chemotherapy in recurrent/metas...

Authors: Jia-Wei Lv, Jun-Yan Li, Lin-Na Luo, Zi-Xian Wang and Yu-Pei Chen

Remembering the forgotten child: the role of immune checkpoint inhibition in patients with human immunod eficiency virus and cancer

Patients with human immunodeficiency virus (HIV) infection have a high risk of developing virally-mediated cancers. These tumors have several features that could make them vulnerable to immune checkpoint inhib...

Authors: Jacob J. Adashek, Pedro Nazareth Aguiar Junior, Natalie Galanina and Razelle Kurzrock

First-line treatment for patients with advanced non-small cell lung carcinoma and high PD-L1 expression: pembrolizumab or pembrolizumab plus chemotherapy

Pembrolizumab monotherapy has become the preferred treatment for patients with advanced non-small cell lung carcinoma (NSCLC) and a programmed cell death-ligand 1 (PD-L1) tumor proportion score (TPS) of at lea...

Authors: Yixin Zhou, Zuan Lin, Xuanye Zhang, Chen Chen, Hongyun Zhao, Shaodong Hong and Li Zhang

Treatment of malignant pleural effusions: the case for localized immunotherapy

Malignant pleural effusions (MPE) are a common terminal pathway for many cancers, with an estimated United States incidence of more than 150,000 cases per year. MPE is an aggressive disease with a uniformly fa...

Authors: Albert D. Donnenberg, James D. Luketich, Rajeev Dhupar and Vera S. Donnenberg

Could the menagerie of the gut microbiome really cure cancer? Hope or hype

The investigational scale of the gut microbiome is expanding rapidly. In 2018, the intersection of gut microbiota and immuno-oncology received much attention. While the impact of gut microbiota on the immune s...

Authors: Muhammad Bilal Abid

Radiotherapy enhances responses of lung cancer to CTLA-4 blockade

Formenti et al. have recently reported the clinical outcomes and translational readouts of a trial of the anti-CTLA-4 inhibitor, ipilimumab, in combination with palliative radiotherapy in 39 patients with non-...

Authors: Anna Wilkins, Fiona McDonald, Kevin Harrington and Alan Melcher

Two roads for oncolytic immunotherapy development

Oncolytic viruses are an emerging class of immunotherapy agents for cancer treatment. In this issue of JITC, Machiels et al. reports early phase data from an oncolytic adenovirus given by intravenous (IV) admi...

Authors: Howard L. Kaufman and Praveen K. Bommareddy

High and low mutational burden tumors versus immunologically hot and cold tumors and response to immune checkpoint inhibitors

Tumors responding to immune checkpoint inhibitors (ICIs) have a higher level of immune infiltrates and/or an Interferon (IFN) signature indicative of a T-cell-inflamed phenotype. Melanoma and lung cancer demon...

Authors: Saman Maleki Vareki

Taking the bull by the horn: the frontline use of infliximab for the treatment of immune checkpoint inhibitor-induced enterocolitis

Immune checkpoint inhibitors which activate the host’s immune system to fight cancer have brought dramatic improvements to the overall survival of a growing number of deadly malignancies. Their use comes at th...

Authors: Khashayar Esfahani

Treatment duration with immune-based therapies in Cancer: an enigma

Unlike chemotherapy treatments that target the tumor itself (rather nonspecifically), immune-based therapies attempt to harness the power of an individual patient’s immune system to combat cancer. Similar to c...

Authors: Shanta Bantia and Nirmal Choradia

Immune checkpoint inhibitor-related acral vasculitis

Commentary on « Ipilimumab induced vasculitis » by Padda A. et al., J Immunother Cancer. 2018;6:12. The authors diagnosed a small vessel vasculitis following treatment with anti-CTLA-4 (ipilimumab) for a resec...

Authors: Thibault Comont, Vincent Sibaud, Loïc Mourey, Pierre Cougoul and Odile Beyne-Rauzy

The age of enlightenment in melanoma immunotherapy

An updated survival analysis by Callahan et al. published in the February 1, 2018 issue of the Journal of Clinical Oncology reported a 3-year overall survival (OS) rate of 63% for 94 patients with previously trea...

Authors: Mark R. Albertini

A team effort: natural killer cells on the first leg of the tumor immunity relay race

Recent work by Böttcher and colleagues defines a new role for Natural Killer cells in the anti-tumor immune response, arriving early into the tumor microenvironment before passing the baton to DC1 dendritic ce...

Authors: Timothy B. Fessenden, Ellen Duong and Stefani Spranger

Oxidized lipids keep heat shock chaperones busy: new insights on the deficiencies of tumour-associated dendritic cells

In a recent publication in Nature Communications the group of Dr. Dmitry Gabrilovich takes us one step closer to understanding why lipid accumulation impairs the function of tumour-associated dendritic cells (DCs...

Authors: Paula Nunes-Hasler

Immune oncology, immune responsiveness and the theory of everything

Anti-cancer immunotherapy is encountering its own checkpoint. Responses are dramatic and long lasting but occur in a subset of tumors and are largely dependent upon the pre-existing immune contexture of indivi...

Authors: Tolga Turan, Deepti Kannan, Maulik Patel, J. Matthew Barnes, Sonia G. Tanlimco, Rongze Lu, Kyle Halliwill, Sarah Kongpachith, Douglas E. Kline, Wouter Hendrickx, Alessandra Cesano, Lisa H. Butterfield, Howard L. Kaufman, Thomas J. Hudson, Davide Bedognetti, Francesco Marincola…

Viruses, bacteria, and parasites – oh my! a resurgence of interest in microbial-based therapy for cancer

As infections and cancer are two of the most common maladies affecting human beings, a concerted effort is needed to better understand their potential interactions and to further explore their use in microbial...

Authors: Andrew Zloza

Transplanters drive CARs to the clinic by brewing ICE-T: the Moffitt roadmap

Recent single institution clinical trial successes with anti-CD19 Chimeric Antigen Receptor (CAR) T cell therapy for B cell malignancies attracted significant attention from industry. Our center sought to rapi...

Authors: Frederick L. Locke and Claudio Anasetti

Sudden hearing loss in a melanoma patient on pembrolizumab: an etiology not to be omitted in the differential diagnosis

Immune checkpoint inhibitors have emerged as a promising therapeutic option for metastatic cancers. However, they have been associated with inflammatory adverse reactions in various organ systems. A recent art...

Authors: Marc-Elie Nader, Jeffrey N. Myers and Paul W. Gidley

FAK-inhibition opens the door to checkpoint immunotherapy in Pancreatic Cancer

Immunotherapy has had remarkable success in the treatment of some cancer types. However, pancreatic cancer has remained largely refractory to immunotherapy, including immune checkpoint inhibitors. Recently, Ji...

Authors: Stefan N. Symeonides, Stephen M. Anderton and Alan Serrels

Immunotherapy resistance: the answers lie ahead – not in front – of us

Mechanisms of innate and adaptive resistance to checkpoint blockade immunotherapy are under intense investigation with a view to broadening the therapeutic potential of this form of treatment. In a recent manu...

Authors: Miles C. Andrews and Jennifer A. Wargo

It’s a long way to the top (if you want to personalize immunotherapy)

Harnessing the immune system to attack tumor cells by targeting tumor-associated or –preferably– tumor-specific antigens has emerged as a promising but challenging treatment option for malignant lymphomas. Fol...

Authors: Sarah Haebe and Oliver Weigert

Potassium channels of T lymphocytes take center stage in the fight against cancer

A recent study by Eil at al. published in Nature in September 2016 provides evidence that alterations of the K⁺ homeostasis of tumor infiltrating lymphocytes (TILs) in necrotic areas of the tumor microenvironment...

Authors: Laura Conforti

Being “penny-wise but pound foolish” in cancer immunotherapy research: the urgent need for mouse cancer models to reflect human modifying factors

Inbred mice are the mainstay for preclinical cancer assessment of potential therapeutics, especially immune-based approaches. However, the use of young, lean, inbred mice housed under specific-pathogen-free co...

Authors: William J. Murphy

A quantum leap in cancer vaccines?

Authors: Eli Gilboa

Application of the Immunoscore as prognostic tool for hepatocellular carcinoma

To date, the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) tumor, nodes, metastasis (TNM) classification represents the standard system for evaluation of progn...

Authors: Annacarmen Petrizzo and Luigi Buonaguro

Re-discovering NK cell allo-reactivity in the therapy of solid tumors

Authors: Luca Castagna and Domenico Mavilio

Circulating protein and antibody biomarker for personalized cancer immunotherapy

Immune checkpoint blockade therapies are revolutionizing standard cancer treatments. Immune checkpoint inhibitors likely function to enhance the tumor specific antigen response in order to achieve favorable cl...

Authors: Jianda Yuan

It’s TIME for a biomarker-driven approach to cancer immunotherapy

Authors: Leisha A. Emens

Cancer immunotherapy trials: leading a paradigm shift in drug development

Authors: Leisha A. Emens, Lisa H. Butterfield, F. Stephen Hodi Jr., Francesco M. Marincola and Howard L. Kaufman

NLRC5, a promising new entry in tumor immunology

The recent use of T cell-based cancer immunotherapies, such as adoptive T-cell transfer and checkpoint blockade, yields increasing clinical benefit to patients with different cancer types. However, decrease of...

Authors: Sonia T. Chelbi and Greta Guarda

Society for immunotherapy of cancer (SITC) statement on the proposed changes to the common rule

The Common Rule is a set of ethical principles that provide guidance on the management of human subjects taking part in biomedical and behavioral research in the United States. The elements of the Common Rule ...

Authors: Howard L. Kaufman, Lisa H. Butterfield, Pierre G. Coulie, Sandra Demaria, Robert L. Ferris, Jérôme Galon, Samir N. Khleif, Ira Mellman, Pamela S. Ohashi, Willem W. Overwijk, Suzanne L. Topalian and Francesco M. Marincola

How do I steer this thing? Using dendritic cell targeted vaccination to more effectively guide the antitumor immune response with combination immunotherapy

Mounting an immune response sufficient to eradicate a tumor is the goal of modern immunotherapy. Single agent therapies with checkpoint inhibitors or costimulatory molecule agonists are effective only for a sm...

Authors: Stefanie N. Linch and William L. Redmond

Immune-related response evaluations during immune-checkpoint inhibitor therapy: establishing a “common language” for the new arena of cancer treatment

The recent study by Hodi et al. published in the Journal of Clinical Oncology has evaluated unconventional response patterns during PD-1 inhibitor therapy using immune-related response criteria (irRC) in compa...

Authors: Mizuki Nishino

Can abscopal effects of local radiotherapy be predicted by modeling T cell trafficking?

The abscopal effect of radiation describes tumor regression in metastases outside of the field upon treatment of one site, and is mediated by radiation-induced anti-tumor T cells. The ability of radiation to g...

Authors: Sandra Demaria and Silvia C. Formenti

Targetless T cells in cancer immunotherapy

Attention has recently focused on new cancer immunotherapy protocols aiming to activate T cell mediated anti-tumor responses. To this end, administration of antibodies that target inhibitory molecules regulati...

Authors: Per thor Straten and Federico Garrido

Natural killer cell immunotherapy to target stem-like tumor cells

Advances in cancer immunotherapy are leading to its increasing and successful application for the treatment of solid–tissue cancers. Despite the recent advances there are still significant barriers, in particu...

Authors: Steven K. Grossenbacher, Robert J. Canter and William J. Murphy

A role for pre-mNK cells in tumor progression

The innate and adaptive immune systems have evolved together to fight infection and cancerous tissues. The innate immune system emerges first with the adaptive immune system following, both ostensibly being br...

Authors: Carolyn Rosinsky and Paul Andrew Antony

Chimeric antigen receptor-engineered T cells in CLL: the next chapter unfolds

The long-standing promise for the application of engineered T lymphocytes to target and eradicate malignancy has begun to be realized recently, with remarkable clinical success reported by a number of groups u...

Authors: Michael Kalos

The dark side of ID8-Luc2: pitfalls for luciferase tagged murine models for ovarian cancer

Reliable mouse models are key in the discovery and development of novel anticancer treatments. Non-invasive monitoring techniques such as bioluminescence imaging (BLI) are useful tools to determine tumor engra...

Authors: Thaïs Baert, Tina Verschuere, Anaïs Van Hoylandt, Rik Gijsbers, Ignace Vergote and An Coosemans

A new paradigm for tumor immune escape: β-catenin-driven immune exclusion

Increasing evidence is emerging that immunotherapeutic interventions, including checkpoint blockade, are predominantly effective in patients with a pre-existing T cell-inflamed tumor microenvironment. Understa...

Authors: Stefani Spranger and Thomas F. Gajewski