Preexisting tumor-resident T cells with cytotoxic potential associate with response to neoadjuvant anti–PD-1 in head and neck cancer

• DOI: 10.1126/sciimmunol.adf4968
• Publication Date: 2023-09-08T17:58:21Z
• 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. Schoe...; 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
• Keywords: Tumor-infiltrating lymphocytes; Neoadjuvant Therapy

About 50% of patients with locally advanced head and neck squamous cell carcinoma (HNSCC) experience recurrences after definitive therapy. The presurgical administration anti-programmed death protein 1 (PD-1) immunotherapy results in substantial pathologic tumor responses (pTR) within the microenvironment (TME). However, mechanisms underlying dynamics antitumor T cells upon neoadjuvant PD-1 blockade remain unresolved, approaches to increase are lacking. In a phase 2 trial (NCT02296684), we observed that 45% treated two doses pembrolizumab experienced marked pTRs (≥50%). Single-cell analysis 17,158 CD8