Masters of Immunology
Melvyn T. Chow and Andrew D. Luster
Cancer Immunol Res December 1 2014 2 (12) 1125-1131; DOI:10.1158/2326-6066.CIR-14-0160
Tanimine and colleagues report that multiplicity of compound KIR-HLA genotypes in blood cells of patients with hepatocellular carcinoma (HCC) correlate with HCC recurrence, supporting therapeutic manipulation of NK-cell activity to compensate for genetic susceptibility to HCC recurrence.
Bordry and colleagues report on a patient with metastatic melanoma, who received repetitive vaccinations with melanoma-associated antigen peptides augmented with CpG as adjuvant, developed autoimmunity without clinical complication, and experienced complete remission and long-term survival for more than 13 years.
Kibe and colleagues report the safety and benefit in a phase II study of 60 pretreated, advanced colorectal cancer (CRC) patients of personalized vaccines comprising HLA-matched peptides selected from preexisting host immunity, providing a new approach of personalized immunotherapy for refractory CRC.
Fend and colleagues show in an orthotopic mouse model of renal carcinoma that intravenous and not subcutaneous injection of an MVA-MUC1 vaccine with TLR9 ligand (ODN1826) controls tumor growth by efficiently targeting tumor-specific effector/memory lymphocytes to the tumor.
Miller and colleagues demonstrate a mechanism by which splenectomy promotes rejection of intraocular tumors, which involves an IFNg-and-Fas/FasL-dependent interaction between CD8+ T cells and intratumoral macrophages eliciting severe ocular inflammation that indirectly eliminates intraocular tumors by inducing phthsis.
Murray and colleagues used RNAi functional genomics screening of 60 genes from an EGFR gene network and identified that inhibition of c-Abl activity in anti-EGFR-targeted cells can enhance the therapeutic efficacy of cetuximab, an ADCC-promoting anti-EGFR antibody, in colorectal and head and neck cancers.
Ohkuri, Ghosh, Kosaka, and colleagues show that a STING-mediated DNA-sensor signaling is involved in IFN induction in the sterile microenvironment of brain tumor that enhances antitumor immunity, providing a proof-of-concept for developing STING agonists for cancer immunotherapy.
Cheung and colleagues show that hepatic oncofetal protein granulin–epithelin precursor (GEP) regulates HCC immunity by modulating MICA and HLA-E expression, which could be reversed by GEP blockade; serum GEP and MICA levels are prognostic and can be used to stratify patients for targeted therapy.
Mariya and colleagues analyzed 122 cases of epithelial ovarian cancer (EOC) and identified low expression of HLA class I and low intraepithelial CTL infiltration as independent prognostic factors for poor overall survival for patients with advanced EOC; low HLA class I expression was correlated with platinum resistance.
Simon, Omokoko, and colleagues developed an integrated approach to retrieve and functionally characterize TCRs from single viral or tumor Ag-reactive T cells and isolated 56 unique Ag-specific TCRs against 39 different epitopes, supporting rational design of T cell-based immunotherapies using this approach.