Authors: Giacomo Oliveira, Ann Marie Egloff, Alexander B. Afeyan, Jacquelyn O. Wolff, Zexiang Zeng, Rebecca D. Chernock, Liye Zhou, Cameron Messier, Patrick Lizotte, Kathleen L. Pfaff, Kari Stromhaug, Livius Penter, Robert I. Haddad, Glenn J. Hanna, Jonathan D. Schoenfeld, Laura A. Goguen, Donald J. Annino, Vickie Jo, Peter Oppelt, Patrik Pipkorn, Ryan Jackson, Sidharth V. Puram, Randal C. Paniello, Jason T. Rich, Jason Webb, Jose P. Zevallos, Mena Mansour, Jingxin Fu, Gavin P. Dunn, Scott J. Rodig, Jessica Ley, Luc G. T. Morris, Lara Dunn, Cloud P. Paweletz, Dorina Kallogjeri, Jay F. Piccirillo, Douglas R. Adkins, Catherine J. Wu, Ravindra Uppaluri
Published: 2023-09-08
DOI: 10.1126/sciimmunol.adf4968
Source: Full article
About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration of anti–programmed cell death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the tumor microenvironment (TME). However, the mechanisms underlying the dynamics of antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, and approaches to increase pathologic responses are lacking. In a phase 2 trial (NCT02296684), we observed that 45% of patients treated with two doses of neoadjuvant pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis of 17,158 CD8