Making No Escape for Tumors

GRU Cancer Center researchers have identified a previously overlooked mechanism that gives tumors an advantage in evading chemoimmunotherapy – and propose how to prevent this evasion to achieve a lasting curative effect.

A problem in treating cancer is that many anti-cancer drugs, including cyclophosphamide (CTX), work only initially, followed by tumor relapse.   Although CTX is used to stimulate the immune system’s action against tumors, it can also activate cells that suppress immune responses.  Recently published in Cancer Research, a team led by Dr. Gang Zhou, along with Cancer Center colleagues Drs. Lei Huang, Kebin Liu, Andrew Mellor, and David Munn, discovered a mechanism responsible for this suppression.

Using an experimental model of B-cell lymphoma, they show that chemoimmunotherapy (via adoptive transfer of tumor-specific immune cells called CD4+ T cells after CTX treatment) caused an inflammatory response that increased a cell population called monocytes.  The group further provides evidence that the monocytes exert immune suppression (establishing tolerance of the tumor to treatment) through the PD-1/PD-L1 pathway.  Adding another chemotherapeutic agent that targets the therapy-induced monocytes promoted long-term survival in the experimental model.

This research demonstrates a number of approaches to modulate chemoimmunotherapy-induced inflammation, promoting immune sensitivity of tumors. Translating these findings into the clinical setting may provide new strategies toward cure.

[Ding ZC, Lu X, Yu M, Lemos H, Huang L, Chandler P, Liu K, Walters M, Krasinski A, Mack M, Blazar BR, Mellor AL, Munn DH, Zhou G. Immunosuppressive Myeloid Cells Induced by Chemotherapy Attenuate Antitumor CD4+ T-Cell Responses through the PD-1-PD-L1 Axis. Cancer Res. 2014 Jul 1;74(13):3441-53.]

Written by
Allison Brown
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Written by Allison Brown

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