Tuesday, May 19, 2015

Tumors repel immune system but attract lytic viruses

Clinically relevant tumors have two characteristics: uncontrolled proliferation (expansion) and immune evasion.

Surprisingly, several recent papers indicated that tumor transformations are associated with inhibition of cell-autonomous anti-viral/anti-modified RNA/anti-modified DNA recognition pathways such as RIG-I or STING.

First, the authors showed that cancer-associated fibroblast (CAF) showed [TGF-β dependent] increase in sensitivity to virus replication compared normal fibroblast harvested from the same cancer patient.

Next, the authors showed that cancer cells too become susceptible to viral infection when co-cultured with cancer associated fibroblast.

This viral titre enhancement was mediated by soluble factor.

Screen for active factors indicated that enhancing factor was fibroblast growth factor-2 (FGF-2). Indeed, inhibition of FGF-2 by RNAi reduced viral titre in tumor-CAF co-culture.

Finally, the authors showed that virus expressing FGF-2 could induce regression of established tumor in mouse model.

In summary, these results suggest that exploiting cancer vulnerability towards lytic viruses may be an alternative path for biological cancer therapy

Note: It is puzzling that virus targets only cancer cells. The authors explained such selective sensitivity of cancer cells based on reduced baseline anti-viral activity in cancer cells. However, we need to consider the fact that cancer patients maybe immune deficient in general, making them generally susceptible to viral infections.

David Usharauli

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