Insights into Immune System Tolerance to Tumors May Lead to Better Cancer Treatments

The immune system does not destroy tumors even though they express molecules that should activate immune cells.

The immune system is, therefore, reported to be tolerant of the tumors. Several molecules and cell types have been implicated in the induction of immune system tolerance to tumors, including, in laboratory mice, a small population of immune cells known as plasmacytoid dendritic cells (pDCs) that produce the enzyme indoleamine 2,3-dioxygenase (IDO) and that are isolated from the lymph nodes that drain the site of the tumor.

Now, researchers from the Medical College of Georgia (Augusta, GA, USA) have identified how these mouse IDO-expressing pDCs induce tumor-specific immune tolerance. In the study, which appears online on August 16, 2007, in advance of publication in the September 2007 print issue of the Journal of Clinical Investigation, Dr. David Munn and colleagues found that mouse IDO-expressing pDCs from tumor-draining lymph nodes directly activate the suppressive function of a population of regulatory immune cells characterized as CD4+CD25+Foxp3+ and known as Tregs.

Suppression by Tregs activated by IDO-expressing pDCs was mediated by interactions between programmed cell death 1 (PD1) and its ligands. This process of suppression is different from that used by Tregs triggered by other stimuli.

Significantly, immune suppression in tumor-draining lymph nodes was blocked by treating mice with both a chemotherapeutic drug and a chemical inhibitor of IDO, but not either agent alone, leading the investigators to suggest that combining IDO inhibitors with chemotherapeutic agents might improve the effectiveness of chemotherapeutics in individuals with cancer.


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Medical College of Georgia