Negative immune regulation plays a notable role in tumor immunity. This study aimed to
confirm that CD137 mediates negative immunoregulation as well as agonist activity in
tumor immunity. Soluble CD137 (sCD137), a prominent splice variant of membranebound CD137 (mCD137), was identified, and its concentration in the blood of lung cancer
patients was increased. The baseline concentration of sCD137 in the blood was
negatively correlated with the efficacy of neoadjuvant immunochemotherapy in a pilot
study. The percentage of CD137+ regulatory T cells (Tregs) in the blood of lung cancer
patients was also increased, and further enriched at the tumor site; Foxp3, CTLA-4, IL-10,
IL-35-Ebi3, sCD137 and costimulato... More
Negative immune regulation plays a notable role in tumor immunity. This study aimed to
confirm that CD137 mediates negative immunoregulation as well as agonist activity in
tumor immunity. Soluble CD137 (sCD137), a prominent splice variant of membranebound CD137 (mCD137), was identified, and its concentration in the blood of lung cancer
patients was increased. The baseline concentration of sCD137 in the blood was
negatively correlated with the efficacy of neoadjuvant immunochemotherapy in a pilot
study. The percentage of CD137+ regulatory T cells (Tregs) in the blood of lung cancer
patients was also increased, and further enriched at the tumor site; Foxp3, CTLA-4, IL-10,
IL-35-Ebi3, sCD137 and costimulatory molecules expression were also higher, indicating
increased immunosuppressive activity. A high percentage of CD137+ Tregs in the tumor
was associated with worse OS outcomes among patients with high CD137+CD8+ T cell
infiltration levels. Notably, targeting CD137+ Tregs using an engineered CD137 agonist
with wild-type mouse IgG2a Fc clearly decreased the total Treg numbers and eliminated
the tumor in the CT26 model and prolonged the survival rate of a Lewis lung carcinoma
(LLC) model. These results indicated it may be possible to empower CD137 agonist with
ability to abolish CD137-mediated negative regulation to enhance its antitumor efficacy