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JCI early table of contents for Dec. 2, 2013

JCI Journals

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:

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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:

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TITLE: Platelets mediate lympho-venous hemostasis to maintain blood-lymphatic separation throughout life

University of Pennsylvania, Philadelphia, PA, USA
Phone: (215) 898-9007; E-mail:

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TITLE: Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3β

Johns Hopkins University School of Medicine, Baltimore, MD, USA
Phone: 410-955-7153; Fax: 410-502-2558; E-mail:

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TITLE: Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity

University of Miami Miller School of Medicine, Miami, FL, USA

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TITLE: Vaccine-induced monoclonal antibodies targeting circumsporozoite protein prevent Plasmodium falciparum infection

Ghent University and Hospital, Gent, UNK, BEL
Phone: +32476847580; E-mail:

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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:

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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:

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