Study demonstrates the possibility to harness macrophages to fight cancer


The majority of existing cancer immunotherapies manipulate the behavior of T cells, a subtype of white blood cells that belong to the adaptive immune system. Another arm of the body's immune system, the innate immune system, may actually promote the growth of cancer cells. If cancer therapies can harness both the innate and adaptive arms of the immune system, they may create greater therapeutic value.

Now a new research from Dana-Farber Cancer Institute in Massachusetts has revealed that a compound called TMP195 can engage macrophages of the innate immune system to fight breast tumors in mice. In addition, combining the compound with conventional chemotherapy and immunotherapy results in prolonged remission. The findings, which were published online 8 March 2017 in the prestigious journal Nature, may lead to a way to enhance cancer therapy.

Study lead researcher Anthony Letai and colleagues looked at tumor-associated macrophages (TAMs), a group of cells belonging to the macrophage lineage which is found in solid tumors. Under normal conditions, macrophages help the body fight against foreign invaders, clear away damaged tissue, and restore the affected area. But in the tumor microenvironment, these cells often promote tumor growth. Accumulating evidence suggest that TAMs stimulate angiogenesis and enhance tumor cell invasion, motility, and intravasation.

Letai's team previously found that TMP195, a first-in-class selective class IIa histone deacetylase (HDAC) inhibitor, switches human macrophage response by altering gene activity within TAMs. For the present research, they demonstrated in a mouse model of breast cancer that TMP195 changed the tumor microenvironment, caused tumors to shrink, and reduced pulmonary metastases. When TMP195 was combined with chemotherapy drugs or an immunotherapy, the durability of tumor reduction was enhanced. Altogether, the results suggest that it is possible to utilize the anti-tumor potential of macrophages to fight cancer.
 
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