A Spatiotemporal Immunotherapy Strategy with Acoustic Liberation in Esophageal Cancer
Year: 2026
Type: preprint
Abstract: Esophageal cancer remains difficult to control when immune activation is not accompanied by effective access of cytotoxic lymphocytes to malignant tissue. Although immune checkpoint inhibition has improved outcomes in selected patients, the tumor microenvironment may impose spatial barriers that limit immune-cell penetration. This review examines a translational framework that integrates regional immune priming, non-puncture EUS-guided acoustic liberation, and fever-range immune reinforcement Ready-Go-Fever (RGF) into a sequential therapeutic strategy. The framework begins at diagnosis with regional immune priming through an accessible superficial cervical or supraclavicular lymph node using Physical In-situ Lymph Antigenization (PILA), establishing early regional immune surveillance before substantial mediastinal progression. CD8+ T-cell activation is assessed approximately 24–48 hours later. EUS is then used to define tumor extent and radial thickness and to guide non-puncture acoustic treatment. Mechanical tumor disruption may modify tumor accessibility and release tumor-associated antigens and damage-associated molecular patterns. Immediately after acoustic liberation, RGF is proposed to promote trafficking of primed CD8+ T cells into the newly accessible tumor compartment. Experimental evidence indicates that fever-range thermal stress can enhance lymphocyte-endothelial interactions and CD8+ T-cell trafficking into tumors. Antipyretic exposure may therefore represent an important confounder during RGF. The proposed framework integrates immune priming, physical tumor accessibility, and immune-cell trafficking into a single spatiotemporal sequence. Rather than presenting a validated treatment, this review defines a testable translational hypothesis and proposes anatomical, imaging, immunological, and temporal endpoints for its experimental evaluation.
Author: Lee, Li Chung
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7204231334