JITC Digest – February 2016

Inside this Issue

From the Authors
“With the expanding indications for checkpoint inhibitors in oncology, increased vigilance and awareness is needed to detect potential and previously unreported immune-related adverse events," said Dr. Zibelman. "Here we present the first reported case, and successful treatment of autoimmune hearing loss in a patient receiving checkpoint inhibitors for melanoma."

From the Author
"This commentary summarizes and discusses the most comprehensive published data set on the ability of CAR-engineered T cells to target CLL, highlights relevant clinical and correlative observations from this data set, and also contrasts these data with the broader literature related to CAR T cell targeting of hematologic malignancies," said Dr. Kalos.

From the Authors
"Immunotherapies harness a patient’s immune system to kill cancer. Despite unprecedented clinical results with single agent therapies in some patients with established tumors using checkpoint modulators (anti-CTLA4 or anti-PD1) or adoptive T cell transfer therapy, many individuals do not respond long-term to these single approaches," said Dr. Nelson. "Herein, our findings identify how and when to use toll like receptor (TLR) agonists with vaccines and T cell based immunotherapy regimens to durably eradicate large tumors in vivo. Moreover, our work identifies alternative reagents to harmful lymphodepletion that might safely treat patients sensitive to chemotherapy via studying the microbiome. Overall, this article reveals that it is critical to consider when distinct immune therapies are administered to a patient, given that many investigators, including ourselves, believe that the path forward to improved treatment outcome in cancer patients will be through combinatorial approaches."

From the Authors
"Andersen et al. provide a mechanistic explanation for the importance of oxygen in glioma cell culture," said Dr. Olin. "Six years ago, the Ohlfest/Olin laboratory at the University of Minnesota discovered that incubating glioma cells at physiologic (5%) oxygen, as opposed to atmospheric levels typically used, enriches for endogenous adjuvants. Vaccines from these cells enhance cross priming of tumoricidal CD8 T cells and extend survival of glioma bearing mice. The authors, led now by me, concisely demonstrate that physiologic oxygen enriches for expression of monomeric annexin 2, a previously uncharacterized toll-like receptor 2 ligand antagonizes cells significantly enhancing immunogenicity of tumor-derived vaccines. Andersen et al. then establish that the first 30 amino acids, short peptide fragment of the annexin 2 terminus is responsible for immune activity, opening the door for annexin 2 peptide vaccine production."

From the Authors
"This work describes the effect of changes in the tumor antigen processing machinery, due to inflammation at the tumor site, on T lymphocyte recognition of melanoma," said Dr. Woods. "We describe proteasome switching, leading to changes in the surface presented MHC-peptide repertoire, as a little studied mechanism of tumor escape from immunity, and propose that the impact may be more significant than previously thought. Significantly, in human biopsies, we demonstrate a strong association between the presence of TILs and switching from standard to immunoproteaseomes. These studies were part of a travel abstract award winning poster presented at the SITC conference 2015."

From the Authors
"In this short review, we address the various methodological approaches to multiplexed immunohistochemistry, in order to properly inform on the best-practices to achieve detection of multiple biomarkers," said Dr. Stack. "With a readily adoptable approach, the methods discussed can help to elucidate multivariate interactions that occur between immune correlates and tumor cells, in situ. This holds the potential for improving stratification approaches in relation to checkpoint blockade therapies, as well as broadening our understanding of the tumor microenvironment."