Cancer Genetics and Epigenetics 2017, Vol.5, No.7, 33-38
33
Research Report
Open Access
Advances in Molecular Imaging Strategies in Immune Checkpoint Therapy
Mingyu Zhang
1
, Hailong Xu
1
, Hao Jiang
1
, Huijie Jiang
2
1 Department of radiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, 150086, China
2 Department of radiology, the Second Affiliated Hospital of Harbin Medical University, No. 246, Xuefu Road, Nangang District, Harbin, 150086, China
Corresponding author email:
Cancer Genetics and Epigenetics, 2017, Vol.5, No.7 doi:
Received: 11 Dec., 2017
Accepted: 20 Dec., 2017
Published: 29 Dec., 2017
Copyright © 2017
Zhang et al., This is an open access article published under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:
Zhang M.Y., Xu H.L., Jiang H., and Jiang H.J., 2017, Advances in molecular imaging strategies in immune checkpoint therapy, 5(7): 33-38 (doi:
)
Abstract
Tumor cells avoid being detected and eliminated by the innate immune system, and as a result, are able to proliferate in
the body. Immune checkpoint inhibitor therapies eliminate cancer cells by activating immune cells in the body; however, this
treatment is not suitable against all cancer types. This reflects a dire need for the development of non-invasive molecular imaging
tools in the visualization of immune checkpoints expression, which will then allow practitioners to improve clinical assessments,
screen interest groups and provide therapeutic predictions, furthering the development of personalized medicine. Therefore, the
analyzing the efficacy of various tracers and the optimization of antibodies have recently become popular topics of research in the
field of antibody-based imaging. This review summarizes the current mechanism of immune checkpoint-based treatments, and
preclinical studies on immune checkpoint imaging.
Keywords
Immune checkpoints; PD-1/PD-L1; Molecular imaging
Background
Under normal circumstances, immune checkpoints serve as protective agents in the immune system. However,
tumor cells avoid being detected and eliminated by the body’s immune system by overexpressing immune
checkpoint molecules; this allows them to proliferate in the body. In an era when personalized cancer medicine is
advocated, immune checkpoint inhibitor therapy (ICT) stands out uniquely amongst other cancer therapies by
virtue of its nature as a ‘common denominator’. This therapeutic strategy suppresses tumors by inhibiting the
activity of immune checkpoints, while activating the T-cell immune response towards tumor cells. At present, the
most extensively researched immune checkpoint molecules include: cytotoxic T-lymphocyte-associated protein 4
(CTLA-4), programmed cell death protein 1 (PD-1) and PD-L1, as well as B- and T-lymphocyte attenuator
(BTLA), V-domain Ig-containing suppressor of T-cell activation (VISTA), T-cell immunoglobulin and mucin
domain-3 (TIM3), lymphocyte-activation gene 3 (LAG3), etc (Le Mercier et al., 2015). The field of molecular
imaging itself is on the rise, as immune-based molecular imaging of monoclonal antibodies (mAbs) is a
prospective, non-invasive molecular imaging technique. In particular, Immuno-PET imaging uses
positron-emitting isotopes to non-invasively trace and quantify the expression of mAbs, and is capable of
producing high-quality images.
1 Role of T-cell Co-stimulation during the Immune Response
Complete activation of T-cells requires dual signaling, as well as cytokine activity. Initial T-cell activation occurs
during the specific binding of T-cell receptors (TCR) to major histocompatibility complexes (MHC)-antigenic
peptide complexes, constituting the first signal for T-cell activation; the second signal for T-cell activation comes
from the interaction between co-stimulatory molecules expressed on the surface of antigen presenting cells (APCs)
and the corresponding receptors or ligands expressed on the surface of T-cells. Many of these molecules are
members of the B7 family, and act as regulators of immune checkpoints, to either activate or suppress T-cell
activity during the immune response by modulating signaling thresholds. Positive co-stimulatory molecules
function by facilitating T-cell proliferation andacquisition of effector function. CD28 is one such positive
co-stimulatory molecule (immune checkpoint) that facilitates T-cell activation, as the recognition of the CD80 and
CD86 ligands occur on the surfaces of mature APCs. Negative checkpoint regulators (NCRs), on the other hand,
