Cancer Immunology at the Crossroads: Tumor Microenvironment
Wei Liang and Napoleone Ferrara
Cancer Immunol Res February 1 2016 4 (2) 83-91; DOI:10.1158/2326-6066.CIR-15-0313
Macrophages expressing tumor markers were detected in the blood and eye of a patient with parotid gland carcinoma. These “Trojan horses” may transport tumor cells to distant organs, where carcinomas could grow and establish metastases in new environments.
Despite dramatic clinical successes for cancer vaccines and immune checkpoint blockade, disease usually progresses. In a mouse model that combined vaccines with checkpoint blockade, significant CTL activation, tumor eradication, and long-term survival was achieved.
Macrophage migration inhibitory factor (MIF) is produced by monocytes in cancer-bearing mice and humans. MIF was found to be critical for suppressive monocytic cells in melanoma patients, and when inhibited, the monocytic cells acquire antitumor phenotypes.
NK cell–based immunotherapy may be hampered by adaptation to reduced inhibitory input from MHC molecules on surrounding cells. However, while such readjustment of responsiveness leads to tolerance to healthy cells, reactivity to cancer cells remains.
Glioblastoma has been especially challenging to treat. In a systematic analysis of combinations of checkpoint therapies in a murine model, some single and dual immunotherapies increased intratumoral effectors, reduced suppressors, and eliminated the tumors.
A subtype of adult T-cell leukemia cells can be distinguished based on the hypomethylated state of their FOXP3 gene. These cells have Treg properties, and the patients have a poor prognosis.
Intratumoral injection of CTL-stimulatory agents could provide another avenue for immunotherapy. TriMix mRNA, comprising three DC-oriented stimulatory mRNAs, was examined in mouse models and provides a rationale for clinical testing in solid and accessible tumors.
Ovarian cancer would benefit from the identification of early biomarkers of prognostic value. Deep sequence–coupled biopanning identified autoantibody responses to a CA125 epitope in a subset of ovarian cancer patients that correlated with extended survival.
Reports of autoantibodies to survivin in lung cancer sera lead to suggestions of roles as biomarkers. The authors tested patient serum with two approaches, controlling for specificity and using controls stratified for smoking habits. No autoreactivity was found.