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
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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
Journal of Clinical Investigation