David Sher, Vice Chair of Clinical Operations and Quality, Medical Director of Radiation Oncology, Chief of Head and Neck Radiation Oncology Service at UTSW Medical Center, shared a post on X about 2 papers published in Nature Cancer:
“Both of these papers are a must-read.
Well-written (so even non-scientists like myself can follow reasonably well), clear scientific method, and remarkable results.
Bottom-line: high tumor bacterial burden (TBB) is strongly related to response to immune checkpoint blockade, with similar/complementary results in different trials and datasets.
Higher TBB seems to drive a neutrophil/myeloid-heavy microenvironment that is immunosuppressive.
The field has long posited that elective nodal irradiation and RT in general have been the key immune suppressors in non-metastatic trials, but these data are very compelling that the tumor microbiome is the (or one of the) critical drivers of response (as an example, check out the survival curves below).
Amazing work. Bravo!
This work brings up so many future studies/questions.
- Are there samples from KN-689 that can validate these results in the neoadjuvant setting?
- The Silver paper suggested antibiotics can mitigate the immunosuppression from high TBB. Can this strategy work in patients?
- Can a clinically-viable test be developed to assess TBB?
- Do these findings have any relevance for patients with metastatic HNSCC (w/ or w/o disease in the HN)?”
Title: Tumor ecosystem and microbiome features associated with efficacy and resistance to avelumab plus chemoradiotherapy in head and neck cancer
Authors: Nadeem Riaz, Tyler J. Alban, Robert I. Haddad, Michelle Saul, Vladimir Makarov, Yingjie Zhu, Ezra E. W. Cohen, Robert L. Ferris, Peter Mu-Hsing Chang, Jin-Ching Lin, Amanda Psyrri, Prerana Bangalore Parthasarathy, Ardijana Novaj, Mruniya Gawali, Douglas Hoen, Phineas Hamilton, Natalie L. Silver, Ivan Juric, Daniel Chawla, Ana Gradissimo, Jennifer Ko, Daniel J. McGrail, Craig B. Davis, Nancy Y. Lee, Timothy A. Chan
You can read the Full Article in Nature Cancer.
Title: Intratumoral bacteria are immunosuppressive and promote immunotherapy resistance in head and neck squamous cell carcinoma
Authors: Natalie L. Silver, Jin Dai, Travis D. Kerr, Jessica Altemus, Rekha Garg, Hannah Simmons, Tyler Alban, Laura Noel-Romas, Vladimir Makarov, David J. H. Shih, Shwetha V. Kumar, Akeem Santos, Rehan Akbani, Adam Burgener, Mohammed Dwidar, Neil Gross, Andrew G. Sikora, Elias J. Sayour, Apollo Stacy, Christian Jobin, Timothy A. Chan, Renata Ferrarotto, Daniel J. McGrail
You can read the Full Article in Nature Cancer.
More posts featuring David Sher.