Work

Immunobiology of Radiotherapy: New Paradigms

Year: 2014

Type: article

Abstract: It has been well demonstrated that irradiated dying cancer cells release tumor antigens. The extracellular antigens and dying tumor cells are engulfed by circulating bone marrow-derived antigen-presenting cells (APCs). After antigen uptake, APCs migrate to lymph nodes, where they engage with helper T cells for post-stimulation and APC activation. Induction of Th1 response and the activation of APCs further stimulate the induction of tumor specific cytotoxic T lymphocytes (CTLs) that could potentially clear tumor cells both at primary and metastatic sites (Fig. 1). FIG. 1 Schematic representation of the envisioned mechanism of radiation-primed immunotherapy of advanced cancer. Radiation-induced immune modulation happens in two important phases. First, radiation induces damage-associated molecular pattern (DAMP) molecules. In this event, radiation normalizes tumor vasculature, modulates tumor cell phenotype and increases immune recognition of the tumor cell. Radiation treatment can cause: a. upregulation of chemokines and adhesion molecules, providing signals for T cells to be attracted to the tumor; and b. upregulation of MHC molecules and tumor-associated antigens, making it easier for endogenous or immunotherapy-induced T cells to recognize and kill tumor (immunogenic modulation). Second, amplification by abrogating immune checkpoint factors with simultaneous costimulation of effector factors can ultimately lead to the induction of multiple unique T-cell populations (antigen cascade) that can kill antigen disparate tumor cells at metastatic sites (systemic effect) (Fig. 2). FIG. 2 Model for radiation-induced immunogenic modulation.

Source: Radiation Research

DOI: 10.1667/rr13849.1

Authors: Mansoor M. Ahmed, Chandan Guha, James W. Hodge, Elizabeth Jaffee