Predicting outcome for high-dose IL-2 therapy in cancer patients
One of the most potent forms of immunotherapy for patients with metastatic melanoma and renal cell carcinoma is high-dose (HD) bolus IL-2 therapy. Approximately 15% of patients respond to HD IL-2 therapy, with almost 5% going into complete remission; however, use of HD IL-2 therapy is limited due to the toxic effects associated with treatment. Because HD IL-2-associated toxicity is severe, it would be beneficial for clinicians to determine if a patient would respond favorably to this treatment prior to side effect onset. Previous studies indicate that regulatory T cell (Treg) populations increase in patients undergoing HD IL-2 therapy, and in this issue of the Journal of Clinical Investigation , Lazlo Radvanyi and colleagues at M.D. Anderson Cancer Center performed an in depth analysis of Treg populations in melanoma patients undergoing HD IL-2 therapy. The authors identified a distinct population of Treg cells that expressed the inducible T cell costimulator (ICOS) that was highly proliferative following the first cycle of HD IL-2. Furthermore, melanoma patients with greater levels of ICOS+ Tregs in response to HD IL-2 had better clinical outcomes, suggesting that this Treg population may be useful to predict which patients would benefit from HD IL-2.
TITLE: IL-2 therapy promotes suppressive ICOS+ Treg expansion in melanoma patients
AUTHOR CONTACT: Lazlo Radvanyi
University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
Phone: 713.563.9489; E-mail: lradvanyi@mdanderson.org
View this article at: http://www.jci.org/articles/view/46266?key=052e9f45d55cf479c3fe
Blocking antioxidants in cancer cells reduces tumor growth in mice
Many cancers have adapted to cope with high levels of immune system-produced free radicals, also referred to as reactive oxygen species, by overproducing antioxidant proteins. One of these proteins, superoxide dismutase 1 (SOD1), is overproduced in lung adenocarcinomas and has been implicated as a target for chemotherapy. In this issue of the Journal of Clinical Investigation , Navdeep Chandel and colleagues from Northwestern University report the effects of a SOD1 pharmacological inhibitor on non-small-cell lung cancer (NSCLC) cells. The inhibitor, called ATN-224, stunted the growth of human NSCLC cells in culture and induced their death. The researchers also found that ATN-224 inhibited other antioxidant proteins, which caused high levels of hydrogen peroxide inside the cells. The ability of cancer cells to produce hydrogen peroxide was required for ATN-224-dependent effects, because hydrogen peroxide activated cell death pathways. Furthermore, ATN-224 induced cancer cell death and reduced tumor sizes in a mouse model of lung adenocarcinoma. ATN-224 dependent effects in animals were improved when the inhibitor was used in combination with another drug that activates programmed cell death. This study suggests inhibition of antioxidants may be a viable chemotherapeutic option.
TITLE: Targeting SOD1 reduces experimental non–small-cell lung cancer
AUTHOR CONTACT: Navdeep Chandel
Northwestern University, Chicago, IL, USA
Phone: 312-503-2549; Fax: 312-503-0411; E-mail: nav@northwestern.edu
View this article at: http://www.jci.org/articles/view/71714?key=0c483873fa3d4323f67e
ALSO IN THIS ISSUE
TITLE: Platelets mediate lympho-venous hemostasis to maintain blood-lymphatic separation throughout life
AUTHOR CONTACT: Mark L. Kahn
University of Pennsylvania, Philadelphia, PA, USA
Phone: (215) 898-9007; E-mail: markkahn@mail.med.upenn.edu
View this article at: http://www.jci.org/articles/view/70422?key=e0bf1e8b4325529b8506
TITLE: Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3β
AUTHOR CONTACT: David A Kass
Johns Hopkins University School of Medicine, Baltimore, MD, USA
Phone: 410-955-7153; Fax: 410-502-2558; E-mail: dkass@jhmi.edu
View this article at: http://www.jci.org/articles/view/69253?key=fdd04e03e5fcde1d87d4
TITLE: Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity
AUTHOR CONTACT: Eli Gilboa
University of Miami Miller School of Medicine, Miami, FL, USA
E-mail: egilboa@med.miami.edu
View this article at: http://www.jci.org/articles/view/69856?key=b82b38f62d3273213e0a
TITLE: Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection
AUTHOR CONTACT: Lander Foquet
Ghent University and Hospital, Gent, UNK, BEL
Phone: +32476847580; E-mail: lander.foquet@ugent.be
View this article at: http://www.jci.org/articles/view/70349?key=d7a297ecf5c755cf8053
TITLE: Sprouty-2 regulates HIV-specific T cell polyfunctionality
AUTHOR CONTACT: Jonathan Schneck
John Hopkins School of Medicine, Baltimore, MD, USA
Phone: 410-614-4589; E-mail: jschnec1@jhmi.edu
View this article at: http://www.jci.org/articles/view/70510?key=32e2938b962265e8c5b3
TITLE: TTC7A mutations disrupt intestinal epithelial apicobasal polarity
AUTHOR CONTACT: Genevieve de Saint Basile
Institut National de la Santé et de la Recherche Médicale (INSERM), Paris, , FRA
Phone: 33 1 44 38 17 66; E-mail: genevieve.de-saint-basile@inserm.fr
View this article at: http://www.jci.org/articles/view/71471?key=019235d9662f574cd28e
Journal of Clinical Investigation