Data from Neoadjuvant PD-1 Immune Checkpoint Blockade Reverses Functional Immunodominance among Tumor Antigen–Specific T Cells

• DOI: 10.1158/1078-0432.c.6529710.v1
• Publication Date: 2023-04-01T06:19:13Z
• Authors: Jay Friedman; Ellen C. Moore; Paul Zolkind; Yvette Robbins; Paul E. Clavijo; Lilian Sun; Sarah Greene; Megan V. Morisada; Wojciech K. Mydlarz; Nicole Schmitt; James W. Hodge; Hans Schreiber; Carter Van Waes; Ravindra Uppaluri; Clint Allen
• Keywords: Immunodominance; Immune checkpoint; Subdominant; Neoadjuvant Therapy

<div>AbstractPurpose:<p>Surgical resection of primary tumor with regional lymphadenectomy remains the treatment choice for patients advanced human papillomavirus–negative head and neck squamous cell carcinoma. However, even when pathologic disease-free margins can be achieved, locoregional and/or distant disease relapse high. Perioperative immunotherapy may improve outcomes, but mechanistic data supporting use neoadjuvant or adjuvant clinically are sparse.</p>Experimental Design:<p>Two syngeneic models oral cavity carcinoma defined T-cell antigens were treated programmed death receptor 1 (PD-1) mAb before after surgical tumors, antigen-specific responses explored functional <i>in vivo</i> challenge assays.</p>Results:<p>We demonstrated that immunodominance developed among T cells targeting multiple independent antigens. specific subdominant expressed greater levels PD-1. Neoadjuvant, not adjuvant, PD-1 immune checkpoint blockade broke induced to dominant Using tumors lacking immunodominant antigen as a model escape, effector immunity against retaining antigen. When combined complete excision, led formation immunologic memory capable preventing engraftment antigen.</p>Conclusions:<p>Together, these results implicate expression by in mechanism clones within progressing support surgically resectable carcinomas.</p></div>