Page 122 - Read Online

Kiyozumi et al. J Cancer Metastasis Treat 2018;4:31 I http://dx.doi.org/10.20517/2394-4722.2017.77 Page 9 of 15

Figure 2. Immune check point inhibitors in gastric cancer. CTLA-4: cytotoxic T-lymphocyte antige-4; MHC: major histocompatibility
complex; PD-1: programmed death 1; PD-L1: programmed death-ligand 1; TCR: T cell receptor

Other immunotherapies
Other immunotherapies are being verified as potential therapies. Lymphocyte activation gene3 (LAG3),
member of the immunoglobulin superfamily that exerts a wide variety of biological impacts on T cell
function, is another vital checkpoint that is expected to have a synergistic interaction with PD-1/PD-L1.
The combining anti-LAG3 “relatlimab” with nivolumab in patients with solid tumors have been assessed in
clinical trial (NCT01968109). Glucocorticoid-induced TNFR family-related protein (GITR) is expressed at
high levels on regulatory T cells (Treg). The agonist GITR antibody was reported to inhibit Treg-mediated
suppression by eliminating GITR-expressing tumor-infiltrating Treg, or by causing them to become unstable,
thereby attenuating their suppressive activity . This anti-GITR-mAb (TRX518) is also examined in phase
[38]
I trials to determine the safety of treatment in stage III or IV melanoma and other solid tumors including
GC (NCT01239134). These trials are ongoing with reports detailing their results expected in the near future.
Recently, TCR-inducible costimulatory receptor, marker of effector Treg, was a reportedly promising target
for direct Treg-targeted therapeutic agents for GC . From the progress of these research activities, Treg is
[39]
also considered to be an attractive target of treatment for patients with AGC.

Polysaccharide-k (PSK) is a protein-bound polysaccharide isolated from Trametes versicolor. In the past,
addition of PSK to chemotherapy was evaluated to be efficient and its use was attempted in GC treatment
after curative gastrectomy as adjuvant treatment . However, PSK’s clinical benefit was determined to be
[40]
limited; therefore, few studies have included its use in recent years.