Reprogramming Neutrophils to Enhance Cancer Immunotherapy

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A new article published in Science Immunology on February 17, 2023, discussed the immune reprogramming of neutrophils in a breast cancer metastasis model. The article was written by Gong et al., link below. What makes this finding and paper so important? As I have mentioned in my book, the immune system has two sides, one that will attack cancer and the other that will protect it. One critical area that gets less attention than T cells is myeloid cells, part of the innate immune response. Specifically, in this case, we are discussing neutrophils. This article discusses that the PGE2-EP2/EP4 pathway is involved in the recruitment and maintenance of cancer-protecting neutrophils in the lung for breast cancer metastasis. Blocking this pathway at the end of EP2/EP4 can reduce these neutrophils and sensitive cancer to the immune system. As we have discussed, NSAIDs such as Ibuprofen, Asprin, and Celebrex inhibit PGE2. However, in this study, Celebrex did not sufficiently block the pathway to affect the neutrophils.

More specific EP2/EP4 inhibition is needed. They also discuss a partial role in blocking IL-1 and IL-6, both upstream regulators. This is an area that we have experience with using anakinra and tocilizumab, also mentioned in my book. As far as an NSAID that blocks, more specifically, EP2/EP4, there are several studies, including one approved for arthritis in dogs about seven years ago. This is certainly an area that needs more investigation, but the addition of EP2/Ep4 inhibitors to immunotherapy may show some benefit.

Jason R. Williams, MD, DABR

Director of Interventional Oncology/Immunotherapy

Williams Cancer Institute

https://www.science.org/doi/full/10.1126/sciimmunol.add5204?et_rid=162353465&utm_campaign=IMMeToc&af=R&et_cid=4602821&utm_medium=email&utm_content=alert&utm_source=sfmc