Faculty Collaboration Database

Radiation-induced remodeling of the T cell landscape in head and neck cancer. Cancer Immunol Immunother 2026 Apr 15;75(5)

Date

04/15/2026

Pubmed ID

41984232

Pubmed Central ID

PMC13083680

DOI

10.1007/s00262-026-04389-w

Scopus ID

2-s2.0-105035819105 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy associated with high recurrence rates and substantial treatment-related morbidity. Radiation therapy remains a central component of the management of locoregional disease. Although radiation directly damages malignant cells through DNA breaks and associated stress pathways, radioresistance remains common, and a proportion of patients continue to develop locoregional recurrence or distant metastasis despite adequate locoregional control. Recent advances in single-cell and spatiotemporal profiling of HNSCC have clarified how radiation alters systemic and intra-tumoral T cell populations and produces a post-radiation tumor microenvironment that provides insufficient support for the robust priming of new tumor-reactive responses. These insights help explain why clinical trials combining radiotherapy with immune checkpoint inhibitors have not reproduced the synergy predicted by preclinical models. At the same time, they point to opportunities to design radiation as a programmable immune adjuvant. In this review, we summarize emerging mechanistic data on radiation-induced remodeling of the T cell landscape, outline the barriers that limit productive immune priming after treatment, and discuss strategies aimed at restoring effective anti-tumor immunity in the post-radiation setting.

Author List

Memon AA, Said I, Norenberg E, Frei A, Foeckler J, Sun F, Dwinell MB, Lochhead RB, Bruening J, Akakpo K, Massey B, Wong SJ, Hematti P, Kearl TJ, Awan MJ, Himburg HA, Zenga J

Authors

Jennifer D. Bruening MD Assistant Professor in the Otolaryngology and Communication Sciences department at Medical College of Wisconsin
Michael B. Dwinell PhD Center Director, Professor in the Microbiology and Immunology department at Medical College of Wisconsin
Peiman Hematti MD Professor in the Medicine department at Medical College of Wisconsin
Heather A. Himburg PhD Professor in the Radiation Oncology department at Medical College of Wisconsin
Tyce J. Kearl PhD, MD Assistant Professor in the Medicine department at Medical College of Wisconsin
Abdullah A. Memon Predoctoral Research Scholar in the Cancer Center department at Medical College of Wisconsin
Fumou Sun PhD Assistant Professor in the Medicine department at Medical College of Wisconsin
Joseph Zenga MS, MD Chief, Associate Professor in the Otolaryngology and Communication Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Head and Neck Neoplasms
Humans
T-Lymphocytes
Tumor Microenvironment