Editors' ChoiceCancer

The enemy within

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Science Translational Medicine  18 Nov 2015:
Vol. 7, Issue 314, pp. 314ec198
DOI: 10.1126/scitranslmed.aad5909

The relationships between humans and their parasites range from friendly coexistence to aggressive attack resulting in the host’s death. The fascinating story by Muehlenbachs et al. is the first-ever description of how a parasite’s disease can spread to the host—with catastrophic consequences for both.

An HIV-positive South American man developed cough, weight loss, and fevers. These symptoms are concerning for malignancy; indeed, imaging revealed multiple lung and liver tumors accompanied by diffusely enlarged lymph nodes. Eventually, the patient succumbed to the fulminant cancer. Numerous tumor biopsies were performed, but the tissues seen under the microscope puzzled the clinicians. Although the nests of invading cells clearly appeared malignant, with bizarre mitotic figures and abnormal nuclei, the cancer cells were notably smaller than surrounding healthy cells. In fact, they did not look human. Additional stains revealed that the cancer cells originated from a dwarf tapeworm (Hymenolepis nana).

Hymenolepis is usually a rather mild-mannered parasite that lives peacefully in small intestines of up to 75 million individuals around the world. Most patients are not aware they have an unwelcome passenger on board because the infestation causes little to no symptoms. Because it was unknown whether and how tapeworms can develop cancer, the investigators surveyed the genomic landscape of this patient’s tumors. Like human cancers, the metastatic flatworm cells acquired mutations within candidate cell cycle and maturation genes. Thus, the mechanism of malignant transformation seems similar in humans and invertebrates.

How did the tapeworm cells metastasize to human organs? The HIV infection was likely to blame, because the virus incapacitated the patient’s immune response. Detailed exploration of cancers in other immunosuppressed individuals may reveal other surprising links between the immune system and malignancies. This provocative case provides new insights into the never-ending play between humans and the parasites that incessantly assault us from inside and out.

A. Muehlenbachs et al., Malignant transformation of Hymenolepis nana in a human host. N. Engl. J. Med. 373, 1845–1852 (2015). [Abstract]

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