Editors' ChoiceCancer Immunotherapy

Unexpected innate immunity targets for cancer

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Science Translational Medicine  20 May 2015:
Vol. 7, Issue 288, pp. 288ec80
DOI: 10.1126/scitranslmed.aac4991

Chronic inflammation, a hallmark of the innate immune system, promotes tumor growth and metastasis, yet new immunotherapy treatments for cancer usually target the adaptive immune system. New therapies are needed therefore for inflammation-related cancers, many associated with microbes—colon (dysbiosis), gastric (Helicobacter pylori), or head and neck (oral bacteria or yeast).

A recent study by Farnebo et al. showed that targeting the innate immune receptor TLR2 in head and neck cancer may be one such approach. Colonization of the oral cavity with microbes or yeast occurs along with epithelial dysplasia, and microbial colonization of lesions is associated with progression to cancer. The authors showed that a yeast-derived TLR2 agonist, zymosan, promotes tumor growth. Zymosan activated both ERK and NF-κB, suggesting that it had downstream effects on both inflammatory cytokine production and cell proliferation. Human tumor tissues had high expression of TLR2, and activation of TLR2 led to growth of human organoid head and neck cancer cultures. The authors confirmed that TLR2 is a promising drug target by showing that anti-TLR2 antibodies markedly reduced tumor growth in organoid cultures when administered alone and inhibited organoid growth when given along with the TLR2 agonist. Last, pre-treatment of human tumor cells with anti-TLR2 drastically inhibited in vivo growth in xenograft mouse models.

The next step will be to test this approach in vivo with a full, functioning immune system. Nevertheless, the results are a promising step toward identifying innate immune targets for infection- and inflammation-associated cancers. In another publication, the same group demonstrated a role for TLR2/MyD88 in promoting growth of breast and colon stem-like cell populations, indicating that drug targets in the innate immune system may prove useful in a variety of cancers.

L. Farnebo et al. , Targeting Toll-like receptor 2 inhibits growth of head and neck squamous cell carcinoma. Oncotarget 6, 9897–9907 (2015). [Abstract]

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