Latest Articles Now Available in the September Issue
of the Journal for ImmunoTherapy of Cancer
The latest issue of the Journal for ImmunoTherapy of Cancer (JITC) features two new articles from SITC members and presents information in combination cancer immunotherapy. Find brief abstracts from the articles below, and read the issue in its entirety at: www.immunotherapyofcancer.org.
Rational Combinations of Immunotherapeutics That Target Discrete Pathways
Spranger S and Gajewski T
Journal for ImmunoTherapy of Cancer 2013, 1:16 (23 September 2013)
An effective anti-tumor immune response requires the coordinated action of the innate and adaptive phases of the immune system. Critical processes include the activation of dendritic cells to present antigens, produce cytokines including type I interferons, and express multiple costimulatory ligands; induction of a productive T cell response within lymph nodes; migration of activated T cells to the tumor microenvironment in response to chemokines and homing receptor expression; and having effector T cells gain access to antigen-expressing tumor cells and maintain sufficient functionality to destroy them. However, tumors can become adept at escaping the immune response, developing multiple mechanisms to disrupt key processes.
"Multiple immunotherapeutic strategies and agents are gaining traction clinically and since multiple immune regulatory pathways control anti-tumor immune responses, there is a strong rationale to pursue combination immunotherapies," Thomas Gajewski, MD, PhD, corresponding author on the paper, said. "However, with the increasing number of agents being developed, an empiric approach to combination therapy drug development is not tenable. In this review, we propose a logical approach for evaluating immunotherapy combinations, based on distinct mechanisms of action and preclinical models and suggest that this framework might have utility in prioritization of clinical trials of combination approaches, ultimately toward the benefit of cancer patients."
Click here to read the full abstract and article in JITC.
Turning T cells on: Epigenetically Enhanced Expression of Effector T-cell Costimulatory Molecules on Irradiated Human Tumor Cells
Kumari A, Cacan E, Greer SF and Garnett-Benson C
Journal for ImmunoTherapy of Cancer 2013, 1:17 (23 September 2013)
Sub-lethal doses of radiation can alter the phenotype of target tissue by modulating gene expression and making tumor cells more susceptible to T-cell-mediated immune attack. We have previously shown that sub-lethal tumor cell irradiation enhances killing of colorectal carcinoma cells by tumor-specific cytotoxic T cells by unknown mechanisms. Recent data from our lab indicates that irradiation of tumor cells results in the upregulation of OX40L and 41BBL, and that T cells incubated with irradiated tumor cells displayed improved CTL survival, activation and effector activity. The objective of this current study was to determine the mechanism of enhanced OX40L and 41BBL expression in human colorectal tumor cells.
"In this article, we hypothesized that radiation changes the epigenetic landscape of OX40L and of 41BBL promoters in human tumor cells and focus on describing a novel gene regulatory mechanism by epigenetic modifiers in response to irradiation," Charlie Garnett-Benson, PhD, and Susanna Greer, corresponding authors on the paper said. "Our proven hypothesis suggests that such mechanisms of gene expression could be useful in combinatorial therapeutic approaches to modulate these important T-cell signals. The use of ionizing radiation to specifically enhance cancer immunotherapy (CIT) strategies through epigenetic modulation of genes stimulatory to CTLs could have a broad impact on cancer therapy approaches and extend the use of radiation into new directions."
Click here to read the full abstract and article in JITC.
Free Article Submission for SITC Members!
SITC members have only a few months left to take advantage of free manuscript submission in JITC, a $2,230 USD value. Submit your research before the end of 2013 to take advantage of this member benefit.
JITC is accepting submissions from both SITC members and non-members alike in the following categories:
- Basic Tumor Immunology - including Tumor antigens, innate and adaptive anti-tumor immune mechanisms, immune regulation, immune response, cancer and inflammation, preclinical models, chemotherapy and radiotherapy interactions with the anti-tumor immune response, oncolytic viruses
Section Editor: Cornelis J.M. Melief, MD, PhD, ISA Therapeutics BV
- Clinical/Translational Cancer Immunotherapy - including First in man clinical trials, phase II/III clinical studies, immune monitoring investigations, tumor microenvironment, host genetics and clinical outcome, updates on clinical trials
Section Editor: F. Stephen Hodi, Jr., MD, Dana-Farber Cancer Institute
- Immunotherapy Biomarkers - including Predictive/prognostic biomarker studies, gene expression studies in cancer immunotherapy, serological immune biomarkers, multiparameter flow cytometry-defined immune biomarkers, high content immunohistological studies
Section Editor: Lisa H. Butterfield, PhD, University of Pittsburgh Cancer Institute
- Reviews/Editorials - Triggering discussion on hot topics and innovative concepts
Section Editors: Bernard A. Fox, PhD, Earle A. Chiles Research Institute
Thomas F. Gajewski, MD, PhD, University of Chicago
JITC Editor-in-Chief
Pedro J. Romero, Ludwig Center for Cancer Research
To submit your research visit: www.sitcancer.org/journal.
Highly Accessed Article Update 
The article, Primer on Tumor Immunology and Cancer Immunotherapy by Timothy J. Harris and Charles G. Drake has reached highly accessed status with over 1,600 views since its publication in JITC on July 29, 2013. Congratulations to these authors! This paper is a meeting review from the SITC 2012 Primer, a program that is back by popular demand as part of the SITC 2013 Annual Meeting & Associated Programs. For more information on the program and to register, visit: www.sitcancer.org/2013.
